AIM To conduct a review of "interferon related pericarditis". METHODS We searched MEDLINE, EMBASE, Cinahl, and the Co-chrane Database from the earliest available date through September 2016. A search strateg...AIM To conduct a review of "interferon related pericarditis". METHODS We searched MEDLINE, EMBASE, Cinahl, and the Co-chrane Database from the earliest available date through September 2016. A search strategy using the Medical Subject Headings and text keywords "interferon" and "pericarditis" were used. RESULTS Nine case reports were eligible for the present study. Six of 8 cases were women and the mean age was 43.8 ± 13.8 years with chronic hepatitis C in 6 cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case. The patients complained of chest pain in 6 cases, dyspnea in 5 cases and edema in 2 cases. Pericardial friction rub was heard in 3 of 9 cases. Congestive heart failure occurred in 3 of 9 cases. Two mechanisms for pericarditis were demonstrated, one is autoimmune included lupus like syndrome in 2 cases and the other is cardio toxicity in 4 cases. Treatment of interferon related pericarditis is discontinuation of Interferon treatment. Four of 9 cases were treated with prednisone and 4 with nonsteroidal anti-inflammatory drugs. CONCLUSION Interferon related pericarditis still remains uncertain. Treatment of interferon related pericarditis rests mainly on early recognition and drug discontinuation. Interferon related pericarditis was treated with steroid and/or nonsteroidal anti-inflammatory drugs.展开更多
Objective: To investigate the in vitro cleavage ability and effects on apoptosis and cell growth of the bcr-abl fusion gene specific multi-unit ribozymes. Methods: Three fusion point specific ribozymes were designed ...Objective: To investigate the in vitro cleavage ability and effects on apoptosis and cell growth of the bcr-abl fusion gene specific multi-unit ribozymes. Methods: Three fusion point specific ribozymes were designed and the multi-unit ribozymes?in vitro transcription vector and retroviral vector were constructed. The in vitro cleavage ability was tested. The retroviral vector was transfected into K562 cell and the effects on proliferation, apoptosis, cell cycle and cell structure were observed. Results: Multi-unit ribozymes had in vitro cleavage efficiency of 70.8%, which was more efficient than single-unit and double-unit ribozymes. Transfection of the retroviral vector of the ribozyme into K562 cells, induced inhibition of cell growth and apoptosis. The incorporation rate of DNA in ribozymes transfected K562 cells was greatly decreased along with time passed, with an inhibition rate of more than 50% after 96 h of transfection. Under FCM, 18.4% of the cells underwent apoptosis 72 h after transfection and more cells were blocked in G phase, with the ratio in S phase greatly decreased (41.9%). Under electron microscope, compaction of nuclear chromatin and apoptosis bodies were observed. Conclusion: Multi-unit ribozymes specific to bcr-abl fusion gene can be used to treat CML and to purge bone marrow for self-grafting.展开更多
Telomerase activity and the expression of telomerase subunits (for example, telomerase reverse transcriptase and telomerase associated protein 1 and telomerase RNA component) of peripheral white blood cells were detec...Telomerase activity and the expression of telomerase subunits (for example, telomerase reverse transcriptase and telomerase associated protein 1 and telomerase RNA component) of peripheral white blood cells were detected in the patients with acute myelogenous leukaemia (AML) and the correlation between telomerase activity and the expression of telomerase subunits was observed. In 94 peripheral white blood cells from 18 healthy volunteers and 76 patients with AML, including 31 AML at initial presentation, 24 at relapse and 21 at complete remission, the telomerase activity and telomerase subunits mRNA or RNA were detected by PCR ELISA and RT PCR respectively. The results showed that the positive rate of telomerase from patients with AML at initial presentation, at relapse and at complete remission was 74.1 %, 79.2 % and 4.8 % respectively. The positive rate of telomerase reverse transcriptase mRNA from healthy volunteers, AML at initial presentation, AML at relapse and AML at complete remission was 5.6 %, 80.6 %, 83.3 % and 9.5 % respectively. The positive rate of telomerase associated protein 1 mRNA and telomerase RNA component in all samples were 100 %. It was suggested that the up regulation of telomerase activity and the expression of telomerase reverse transcriptase is correlated closely with the occurrence and relapse of AML, so telomerase activity and the expression of telomerase reverse transcriptase may be used to estimate the curative effect and predict relapse of AML. Moreover, the up regulation of telomerase activity is correlated with the expression of telomerase reverse transcriptase significantly.展开更多
Objective:To study the correlation of Aurora family and TRPV family gene expression in acute myelogenous leukemia with disease progression.Methods: Patients who were diagnosed with acute myelogenous leukemia in Kashga...Objective:To study the correlation of Aurora family and TRPV family gene expression in acute myelogenous leukemia with disease progression.Methods: Patients who were diagnosed with acute myelogenous leukemia in Kashgar Prefecture First People's Hospital between January 2014 and September 2017 were selected as the leukemia group of the research, and patients who underwent bone marrow puncture and were without myelogram anomaly in Kashgar Prefecture First People's Hospital during the same time were selected as the control group. The bone marrow tissue was collected to determine the mRNA expression of Aurora family and TRPV family genes, apoptosis genes and metastasis genes.Results: Aurora-A, Aurora-B, Aurora-C, TRPV-5, TRPV-6, GFI-1, Bcl-2, CXCR3, C3AR1,β-arrestin1, MMP2 and MMP9 mRNA expression in bone marrow tissue of leukemia group were significantly higher than those of control group whereas CD40L, Bax, Caspase-9 and Caspase-3 mRNA expression were significantly lower than those of control group. Aurora-A, Aurora-B, Aurora-C, TRPV-5 and TRPV-6 mRNA expression in bone marrow tissue of leukemia group were positively correlated with GFI-1, Bcl-2, CXCR3, C3AR1,β-arrestin1, MMP2 and MMP9 mRNA expression, and negatively correlated with CD40L, Bax, Caspase-9 and Caspase-3 mRNA expression.Conclusion: The high expression of Aurora family and TRPV family genes in acute myelogenous leukemia can promote the proliferation and metastasis of tumor cells during disease progression.展开更多
Objective: This study aimed to report the case of a female patient with chronic myeloid leukemia affected by cryptococcal meningitis. Case report: ML, white, 48 years old, female sex, previously diagnosed with chronic...Objective: This study aimed to report the case of a female patient with chronic myeloid leukemia affected by cryptococcal meningitis. Case report: ML, white, 48 years old, female sex, previously diagnosed with chronic myeloid leukemia that has been refractive to the use of imatinib and who has recently begun using nilotinib, was admitted complaining of sudden and disabling migraine in the last 1 month associated with asthenia, adinamia, anorexia, disinterest for daily activities, dizziness, nausea, and vomiting. She evolved with ataxia, and started to stroll with help and showed decrease of muscular strength in her upper limbs. She also presented episodes of decrease of consciousness, with look fixation, no respond to sound stimulation, and short-term hearing loss. The cerebrospinal fluid showed presence of Cryptococcus sp. and, therefore, we began treatment with intravenous liposomal amphotericin B in the dose of 3 mg/kg/day, for 6 weeks. A new cerebrospinal fluid analysis, at the end of treatment, also showed rare structures that are compatible with Cryptococcus sp. As sequelae, she continued with hearing loss in her right ear and enhancement in her right auditory canal, seen in the magnetic resonance imaging. After stabilization and clinical improvement, she was discharged. After 3 weeks, she was hospitalized again with degeneration of the condition, and died due to intracranial hypertension secondary to cryptococcal infection. Final Considerations: This report reinforces the need of reflecting on fungi pathologies, especially in immunosuppressant patients, as well as the importance of early diagnosing and making a fast intervention, with the aims of providing quality of life and comfort to the patient and of minimizing neurological sequelae to the patient.展开更多
Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue....Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue. It is known to occur more commonly in patients with acute myelogenous leukemia and less commonly in those with myelodysplastic syndrome and myeloproliferative neoplasm, such as chronic myelogenous leukemia. The most common sites of involvement include bone, skin and lymph nodes. However, rare cases have been reported in the gastrointestinal tract, genitourinary tract, or breast. Most commonly, a neoplastic extramedullary proliferation of myeloid precursors in a patient would have systemic involvement of a myeloid neoplasm, including in the bone marrow and peripheral blood. Infrequently, extramedullary disease may be the only site of involvement. It may also occur as a localized antecedent to more generalized disease or as a site of recurrence. Herein, we present the first case in the English literature of a patient presenting with an isolated site of myeloid sarcoma arising in the form of a colonic polyp which, after subsequent bone marrow biopsy, was found to be a harbinger of chronic myelogenous leukemia.展开更多
The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4...The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.展开更多
Objective:To investigate the effects of interferon-a (IFN-a) and IFN-a combined with interleukin-6 (IL-6) on growth and expression of bcr-abl, bcl-2 and c--myc genes in the mononuclear cells (MNCs) from bone marrow (B...Objective:To investigate the effects of interferon-a (IFN-a) and IFN-a combined with interleukin-6 (IL-6) on growth and expression of bcr-abl, bcl-2 and c--myc genes in the mononuclear cells (MNCs) from bone marrow (BM) of patients with chronic myelogenous leukemia (CML). Methods: MNCs were collected from BM of the patients with CML in chronic phase by centrifugation in lymphocyte separation medium and cultured in liquid with IFN-a (200U/ml) or IFN-a (200U/ml) plus IL-6 (100 ng/ml). The growing cells were counted every day. The expression levels of b-actin, bcr-abl, bcl-2 and c-myc genes in the MNCs incubated for 24 h were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and relatively quantitative analysis of the amplified fragments by optical density scanning for the bands on gel. Results: The cell growth was markedly suppressed by IFN-a but the degree of cell-growth inhibition was slightly decreased by IL-6 on the basis of IFN-a effect. The expression of bcr-abl chimeric gene was intensely inhibited by IFN-a or IFN-a plus IL-6. The expression of bcl-2 gene was suppressed by either IFN-a or IFN-a plus IL-6, whereas that of c-myc gene was also inhibited by IFN-a but strongly elevated by IL-6 on the basis of IFN-a action. Conclusions: Both IFN-a and IFN-a plus IL-6 can inhibit the expression of anti-apoptosis gene such as bcr-abl and bcl-2 and regulate the expression of the cs.hn.cn gene related to cell proliferation and differentiation such as c-myc. Either IFN-a or IFN-a combined with IL-6 will serve as a trustful strategy of clinical treatment for CML.展开更多
We developed two complement-fixing MoAbsHIMand HIM(murine)that were specifically reac-tive with chronic myelogenous leukemia (CML) cells.They were capable of fixing human or rabbit com-plement and suitable for CML cel...We developed two complement-fixing MoAbsHIMand HIM(murine)that were specifically reac-tive with chronic myelogenous leukemia (CML) cells.They were capable of fixing human or rabbit com-plement and suitable for CML cells purging of re-mission marrow from CML patients.HIMreactedwith majority leukemic cells form 7 out of 10 CMLpatients by complement-mediated cytotoxicity(C’MC)assay(positive cells 80%—90%),HIMreacted withmajority CML cells from 4 out of 5 CML by C’MCassay(positive cells 80%—90%).Treatment withHIMor HIMand human C’was capable of lysing97% of K562,U937,HL-60 and CML cells in a 20fold excess of unrelated cells by indirect FITC+EBstain.Using limited dilution culture,incubation withHIMand C’produced 1.5 logs inhibition of growthin K562 cells,and 1.9 logs in U937 cells,and withHIMand C’produced 2.9 logs inhibition in HL-60cells and 3.0 logs in U937 cells.Both MoAbs cocktailwas shown 1.8 logs in K562 cells and 3.2 logs in U937cells.They were no suppression on the growth o展开更多
Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoprotei...Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-JAK2 and TEL-PDGFRβ fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed.展开更多
DNA from 36 patients with chronic myelogenous leukemia (CML) at various clinical stages and 6 cases of acute leukemia was investigated for alterations of the p53 gene by Southern blot analysis.Rearrangements of the p5...DNA from 36 patients with chronic myelogenous leukemia (CML) at various clinical stages and 6 cases of acute leukemia was investigated for alterations of the p53 gene by Southern blot analysis.Rearrangements of the p53 gene were seen in 3 of 12 (25.00%) cases of blast crisis and accelerated phase (AP) of CML and in only one of 18 chronic phrase (CP),just as has been reported previously. Meanwhile,by restriction fragment length polymorphism (RFLP) analysis the Bgl II site polymorphism in the p53 gene was also found. The frequency in Chinese people detected here was 0.392,which was strikingly higher than that in some other countries(P<0. 001).These results suggested that the alterations of the p53 gene, for example,p53 rearrangements,were probably responsible for the progression of BC in some CML patients, and that the frequency of Bgl II polymorphism in the p53 gene might be related to the population distribution.展开更多
Clinical trials have demonstrated that some patients with chronic myeloid leukemia(CML)treated for several years with tyrosine kinase inhibitors(TKIs)who have maintained a molecular response can successfully discontin...Clinical trials have demonstrated that some patients with chronic myeloid leukemia(CML)treated for several years with tyrosine kinase inhibitors(TKIs)who have maintained a molecular response can successfully discontinue treatment without relapsing.Treatment free remission(TFR)can be reached by approximately 50%of patients who discontinue.Despite having similar levels of deep molecular response and an identical duration of treatment,the factors that influence the successful discontinuation of CML patients remain to be determined.In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR.We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.展开更多
This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS （surface-enhanced Raman spectroscopy） diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL ...This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS （surface-enhanced Raman spectroscopy） diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL （breakpoint cluster region-Abelson） gene responsible for development of chronic myelogenous leukemia were used as a model system to demonstrate the discrimination between the wild type and Met244Val mutations. The thiolated ssDNA （single-strand DNA） was immobilized on the SERS-active surface and then hybridized to a labeled target sequence from solution. An intense SERS signal of the reporter molecule MGITC was detected from the complementary target due to formation of double helix. The SERS signal was either not observed, or decreased dramatically for a negative control sample consisting of labeled DNA that was not complementary to the DNA probe. The results indicate that our SERS substrate offers an opportunity for the development of novel diagnostic assays.展开更多
The flow cytometric immunoassay was used to study the correlation between the H-ras oncogene product p21 and the DNA ploidy in 30 de novo cases of acute myelogenous leukemia (AML). The results showed that 17 cases wer...The flow cytometric immunoassay was used to study the correlation between the H-ras oncogene product p21 and the DNA ploidy in 30 de novo cases of acute myelogenous leukemia (AML). The results showed that 17 cases were negative for p21 expression and 13 positive for p21. The patients with positive p21 had higher percentage of bone marrow and peripheral blasts and lower peripheral leukocyte count. The expression of p21 had no influence on the therapeutic effect. Before treatment,DNA diploidy occurred in 18 cases including 13 p21 negative ones,and DNA aneuploidy was revealed in 12 cases including 8 p21 positive ones. Patients with positive p21 or having aneuploidy in complete remission were at risk for early relapse. Our results suggest that p21 may be involved in the process of leukemogenesis and progression in AML.展开更多
We report the case of a 52-year-old man with a history of acute myeloid leukemia who presented to the emergency room with fatigue, dyspnea and chest pain. Initial routine examination showed signs of right heart failur...We report the case of a 52-year-old man with a history of acute myeloid leukemia who presented to the emergency room with fatigue, dyspnea and chest pain. Initial routine examination showed signs of right heart failure. A CT was requested to rule out pulmonary embolism. The imaging revealed the presence of a cardiac infiltrative mass involving the heart’s right free wall that proved to be a chloroma.展开更多
BACKGROUND We present a case of focal lymphoblastic transformation to erythroid leukemia following acute myeloblastic transformation in a patient with chronic myelogenous leukemia(CML)and discuss its mechanism of occu...BACKGROUND We present a case of focal lymphoblastic transformation to erythroid leukemia following acute myeloblastic transformation in a patient with chronic myelogenous leukemia(CML)and discuss its mechanism of occurrence and development.CASE SUMMARY The presence of the Philadelphia(Ph)chromosome was identified through karyotype analysis,while the BCR-ABL fusion gene was detected using quantitative real-time polymerase chain reaction of the peripheral blood sample.Fluorescence in situ hybridization was used to detect the expression of the BCRABL gene in the lymphoma.Antigen expression and gene mutations in the primitive cells were detected by flow cytometry.The analysis confirmed the presence of CML along with focal lymphoblastic transformation to erythroid leukemia.Additionally,the patient was found to have secondary erythroid leukemia,along with multiple new gene mutations and abnormalities in complex karyotypes of chromosomes.CONCLUSION Our findings suggest a possible molecular basis for the focal lymphoblastic transformation secondary to myeloblastic transformation in patients with CML.展开更多
Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first-or second-line treatment in imatinib-resistant chronic myelogenous leukemia(CML)pat...Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first-or second-line treatment in imatinib-resistant chronic myelogenous leukemia(CML)patients.Hepatotoxicity due to nilotinib is a commonly reported side effect;however,abnormal liver function test(LFT)results have been reported in asymptomatic cases.When alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels are more than five-fold the upper limit of the normal(ULN)or when the serum total bilirubin level is more than three-fold the ULN,dose modification or discontinuation of nilotinib is recommended,resulting in decreased levels of hematological indicators in certain patients with CML.Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels.Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver.The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity.Therefore,nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia,and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings,physicians should consider maintaining nilotinib dose intensity without modifications.展开更多
970379 Risk of leukemia among diagnostic X-rayworkers in China between 1950 and 1990. WANG Juxi-an(王继先), et al. Radiat Med Instit, CAMS &PUMC, Tianjin, 300192. Chin J Hematol 1997; 18(2):84-86. Objective: To ex...970379 Risk of leukemia among diagnostic X-rayworkers in China between 1950 and 1990. WANG Juxi-an(王继先), et al. Radiat Med Instit, CAMS &PUMC, Tianjin, 300192. Chin J Hematol 1997; 18(2):84-86. Objective: To explore the relationship between radi-展开更多
文摘AIM To conduct a review of "interferon related pericarditis". METHODS We searched MEDLINE, EMBASE, Cinahl, and the Co-chrane Database from the earliest available date through September 2016. A search strategy using the Medical Subject Headings and text keywords "interferon" and "pericarditis" were used. RESULTS Nine case reports were eligible for the present study. Six of 8 cases were women and the mean age was 43.8 ± 13.8 years with chronic hepatitis C in 6 cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case. The patients complained of chest pain in 6 cases, dyspnea in 5 cases and edema in 2 cases. Pericardial friction rub was heard in 3 of 9 cases. Congestive heart failure occurred in 3 of 9 cases. Two mechanisms for pericarditis were demonstrated, one is autoimmune included lupus like syndrome in 2 cases and the other is cardio toxicity in 4 cases. Treatment of interferon related pericarditis is discontinuation of Interferon treatment. Four of 9 cases were treated with prednisone and 4 with nonsteroidal anti-inflammatory drugs. CONCLUSION Interferon related pericarditis still remains uncertain. Treatment of interferon related pericarditis rests mainly on early recognition and drug discontinuation. Interferon related pericarditis was treated with steroid and/or nonsteroidal anti-inflammatory drugs.
基金National Natural Science Foundation of China (No. 39670330).
文摘Objective: To investigate the in vitro cleavage ability and effects on apoptosis and cell growth of the bcr-abl fusion gene specific multi-unit ribozymes. Methods: Three fusion point specific ribozymes were designed and the multi-unit ribozymes?in vitro transcription vector and retroviral vector were constructed. The in vitro cleavage ability was tested. The retroviral vector was transfected into K562 cell and the effects on proliferation, apoptosis, cell cycle and cell structure were observed. Results: Multi-unit ribozymes had in vitro cleavage efficiency of 70.8%, which was more efficient than single-unit and double-unit ribozymes. Transfection of the retroviral vector of the ribozyme into K562 cells, induced inhibition of cell growth and apoptosis. The incorporation rate of DNA in ribozymes transfected K562 cells was greatly decreased along with time passed, with an inhibition rate of more than 50% after 96 h of transfection. Under FCM, 18.4% of the cells underwent apoptosis 72 h after transfection and more cells were blocked in G phase, with the ratio in S phase greatly decreased (41.9%). Under electron microscope, compaction of nuclear chromatin and apoptosis bodies were observed. Conclusion: Multi-unit ribozymes specific to bcr-abl fusion gene can be used to treat CML and to purge bone marrow for self-grafting.
基金ThisprojectwassupportedbyagrantfromthefoundationofscientificandtechnologicalkeyprojectofHubeiProvince (No .2 0 0 2AA30 4B10 )
文摘Telomerase activity and the expression of telomerase subunits (for example, telomerase reverse transcriptase and telomerase associated protein 1 and telomerase RNA component) of peripheral white blood cells were detected in the patients with acute myelogenous leukaemia (AML) and the correlation between telomerase activity and the expression of telomerase subunits was observed. In 94 peripheral white blood cells from 18 healthy volunteers and 76 patients with AML, including 31 AML at initial presentation, 24 at relapse and 21 at complete remission, the telomerase activity and telomerase subunits mRNA or RNA were detected by PCR ELISA and RT PCR respectively. The results showed that the positive rate of telomerase from patients with AML at initial presentation, at relapse and at complete remission was 74.1 %, 79.2 % and 4.8 % respectively. The positive rate of telomerase reverse transcriptase mRNA from healthy volunteers, AML at initial presentation, AML at relapse and AML at complete remission was 5.6 %, 80.6 %, 83.3 % and 9.5 % respectively. The positive rate of telomerase associated protein 1 mRNA and telomerase RNA component in all samples were 100 %. It was suggested that the up regulation of telomerase activity and the expression of telomerase reverse transcriptase is correlated closely with the occurrence and relapse of AML, so telomerase activity and the expression of telomerase reverse transcriptase may be used to estimate the curative effect and predict relapse of AML. Moreover, the up regulation of telomerase activity is correlated with the expression of telomerase reverse transcriptase significantly.
文摘Objective:To study the correlation of Aurora family and TRPV family gene expression in acute myelogenous leukemia with disease progression.Methods: Patients who were diagnosed with acute myelogenous leukemia in Kashgar Prefecture First People's Hospital between January 2014 and September 2017 were selected as the leukemia group of the research, and patients who underwent bone marrow puncture and were without myelogram anomaly in Kashgar Prefecture First People's Hospital during the same time were selected as the control group. The bone marrow tissue was collected to determine the mRNA expression of Aurora family and TRPV family genes, apoptosis genes and metastasis genes.Results: Aurora-A, Aurora-B, Aurora-C, TRPV-5, TRPV-6, GFI-1, Bcl-2, CXCR3, C3AR1,β-arrestin1, MMP2 and MMP9 mRNA expression in bone marrow tissue of leukemia group were significantly higher than those of control group whereas CD40L, Bax, Caspase-9 and Caspase-3 mRNA expression were significantly lower than those of control group. Aurora-A, Aurora-B, Aurora-C, TRPV-5 and TRPV-6 mRNA expression in bone marrow tissue of leukemia group were positively correlated with GFI-1, Bcl-2, CXCR3, C3AR1,β-arrestin1, MMP2 and MMP9 mRNA expression, and negatively correlated with CD40L, Bax, Caspase-9 and Caspase-3 mRNA expression.Conclusion: The high expression of Aurora family and TRPV family genes in acute myelogenous leukemia can promote the proliferation and metastasis of tumor cells during disease progression.
文摘Objective: This study aimed to report the case of a female patient with chronic myeloid leukemia affected by cryptococcal meningitis. Case report: ML, white, 48 years old, female sex, previously diagnosed with chronic myeloid leukemia that has been refractive to the use of imatinib and who has recently begun using nilotinib, was admitted complaining of sudden and disabling migraine in the last 1 month associated with asthenia, adinamia, anorexia, disinterest for daily activities, dizziness, nausea, and vomiting. She evolved with ataxia, and started to stroll with help and showed decrease of muscular strength in her upper limbs. She also presented episodes of decrease of consciousness, with look fixation, no respond to sound stimulation, and short-term hearing loss. The cerebrospinal fluid showed presence of Cryptococcus sp. and, therefore, we began treatment with intravenous liposomal amphotericin B in the dose of 3 mg/kg/day, for 6 weeks. A new cerebrospinal fluid analysis, at the end of treatment, also showed rare structures that are compatible with Cryptococcus sp. As sequelae, she continued with hearing loss in her right ear and enhancement in her right auditory canal, seen in the magnetic resonance imaging. After stabilization and clinical improvement, she was discharged. After 3 weeks, she was hospitalized again with degeneration of the condition, and died due to intracranial hypertension secondary to cryptococcal infection. Final Considerations: This report reinforces the need of reflecting on fungi pathologies, especially in immunosuppressant patients, as well as the importance of early diagnosing and making a fast intervention, with the aims of providing quality of life and comfort to the patient and of minimizing neurological sequelae to the patient.
文摘Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue. It is known to occur more commonly in patients with acute myelogenous leukemia and less commonly in those with myelodysplastic syndrome and myeloproliferative neoplasm, such as chronic myelogenous leukemia. The most common sites of involvement include bone, skin and lymph nodes. However, rare cases have been reported in the gastrointestinal tract, genitourinary tract, or breast. Most commonly, a neoplastic extramedullary proliferation of myeloid precursors in a patient would have systemic involvement of a myeloid neoplasm, including in the bone marrow and peripheral blood. Infrequently, extramedullary disease may be the only site of involvement. It may also occur as a localized antecedent to more generalized disease or as a site of recurrence. Herein, we present the first case in the English literature of a patient presenting with an isolated site of myeloid sarcoma arising in the form of a colonic polyp which, after subsequent bone marrow biopsy, was found to be a harbinger of chronic myelogenous leukemia.
文摘The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.
基金the National Natural Science Foundation of China !(No. 39570805).
文摘Objective:To investigate the effects of interferon-a (IFN-a) and IFN-a combined with interleukin-6 (IL-6) on growth and expression of bcr-abl, bcl-2 and c--myc genes in the mononuclear cells (MNCs) from bone marrow (BM) of patients with chronic myelogenous leukemia (CML). Methods: MNCs were collected from BM of the patients with CML in chronic phase by centrifugation in lymphocyte separation medium and cultured in liquid with IFN-a (200U/ml) or IFN-a (200U/ml) plus IL-6 (100 ng/ml). The growing cells were counted every day. The expression levels of b-actin, bcr-abl, bcl-2 and c-myc genes in the MNCs incubated for 24 h were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and relatively quantitative analysis of the amplified fragments by optical density scanning for the bands on gel. Results: The cell growth was markedly suppressed by IFN-a but the degree of cell-growth inhibition was slightly decreased by IL-6 on the basis of IFN-a effect. The expression of bcr-abl chimeric gene was intensely inhibited by IFN-a or IFN-a plus IL-6. The expression of bcl-2 gene was suppressed by either IFN-a or IFN-a plus IL-6, whereas that of c-myc gene was also inhibited by IFN-a but strongly elevated by IL-6 on the basis of IFN-a action. Conclusions: Both IFN-a and IFN-a plus IL-6 can inhibit the expression of anti-apoptosis gene such as bcr-abl and bcl-2 and regulate the expression of the cs.hn.cn gene related to cell proliferation and differentiation such as c-myc. Either IFN-a or IFN-a combined with IL-6 will serve as a trustful strategy of clinical treatment for CML.
文摘We developed two complement-fixing MoAbsHIMand HIM(murine)that were specifically reac-tive with chronic myelogenous leukemia (CML) cells.They were capable of fixing human or rabbit com-plement and suitable for CML cells purging of re-mission marrow from CML patients.HIMreactedwith majority leukemic cells form 7 out of 10 CMLpatients by complement-mediated cytotoxicity(C’MC)assay(positive cells 80%—90%),HIMreacted withmajority CML cells from 4 out of 5 CML by C’MCassay(positive cells 80%—90%).Treatment withHIMor HIMand human C’was capable of lysing97% of K562,U937,HL-60 and CML cells in a 20fold excess of unrelated cells by indirect FITC+EBstain.Using limited dilution culture,incubation withHIMand C’produced 1.5 logs inhibition of growthin K562 cells,and 1.9 logs in U937 cells,and withHIMand C’produced 2.9 logs inhibition in HL-60cells and 3.0 logs in U937 cells.Both MoAbs cocktailwas shown 1.8 logs in K562 cells and 3.2 logs in U937cells.They were no suppression on the growth o
基金This work was partially supported by a grant from World Health Organization Fellowship (XS) (WPRO AWARD No. 0008/99).
文摘Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-JAK2 and TEL-PDGFRβ fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed.
文摘DNA from 36 patients with chronic myelogenous leukemia (CML) at various clinical stages and 6 cases of acute leukemia was investigated for alterations of the p53 gene by Southern blot analysis.Rearrangements of the p53 gene were seen in 3 of 12 (25.00%) cases of blast crisis and accelerated phase (AP) of CML and in only one of 18 chronic phrase (CP),just as has been reported previously. Meanwhile,by restriction fragment length polymorphism (RFLP) analysis the Bgl II site polymorphism in the p53 gene was also found. The frequency in Chinese people detected here was 0.392,which was strikingly higher than that in some other countries(P<0. 001).These results suggested that the alterations of the p53 gene, for example,p53 rearrangements,were probably responsible for the progression of BC in some CML patients, and that the frequency of Bgl II polymorphism in the p53 gene might be related to the population distribution.
文摘Clinical trials have demonstrated that some patients with chronic myeloid leukemia(CML)treated for several years with tyrosine kinase inhibitors(TKIs)who have maintained a molecular response can successfully discontinue treatment without relapsing.Treatment free remission(TFR)can be reached by approximately 50%of patients who discontinue.Despite having similar levels of deep molecular response and an identical duration of treatment,the factors that influence the successful discontinuation of CML patients remain to be determined.In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR.We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.
文摘This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS （surface-enhanced Raman spectroscopy） diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL （breakpoint cluster region-Abelson） gene responsible for development of chronic myelogenous leukemia were used as a model system to demonstrate the discrimination between the wild type and Met244Val mutations. The thiolated ssDNA （single-strand DNA） was immobilized on the SERS-active surface and then hybridized to a labeled target sequence from solution. An intense SERS signal of the reporter molecule MGITC was detected from the complementary target due to formation of double helix. The SERS signal was either not observed, or decreased dramatically for a negative control sample consisting of labeled DNA that was not complementary to the DNA probe. The results indicate that our SERS substrate offers an opportunity for the development of novel diagnostic assays.
文摘The flow cytometric immunoassay was used to study the correlation between the H-ras oncogene product p21 and the DNA ploidy in 30 de novo cases of acute myelogenous leukemia (AML). The results showed that 17 cases were negative for p21 expression and 13 positive for p21. The patients with positive p21 had higher percentage of bone marrow and peripheral blasts and lower peripheral leukocyte count. The expression of p21 had no influence on the therapeutic effect. Before treatment,DNA diploidy occurred in 18 cases including 13 p21 negative ones,and DNA aneuploidy was revealed in 12 cases including 8 p21 positive ones. Patients with positive p21 or having aneuploidy in complete remission were at risk for early relapse. Our results suggest that p21 may be involved in the process of leukemogenesis and progression in AML.
文摘We report the case of a 52-year-old man with a history of acute myeloid leukemia who presented to the emergency room with fatigue, dyspnea and chest pain. Initial routine examination showed signs of right heart failure. A CT was requested to rule out pulmonary embolism. The imaging revealed the presence of a cardiac infiltrative mass involving the heart’s right free wall that proved to be a chloroma.
基金Supported by Nanjing Military Region Innovation Project,No.15MS108and the Youth Nursery Fund,No.18Y024.
文摘BACKGROUND We present a case of focal lymphoblastic transformation to erythroid leukemia following acute myeloblastic transformation in a patient with chronic myelogenous leukemia(CML)and discuss its mechanism of occurrence and development.CASE SUMMARY The presence of the Philadelphia(Ph)chromosome was identified through karyotype analysis,while the BCR-ABL fusion gene was detected using quantitative real-time polymerase chain reaction of the peripheral blood sample.Fluorescence in situ hybridization was used to detect the expression of the BCRABL gene in the lymphoma.Antigen expression and gene mutations in the primitive cells were detected by flow cytometry.The analysis confirmed the presence of CML along with focal lymphoblastic transformation to erythroid leukemia.Additionally,the patient was found to have secondary erythroid leukemia,along with multiple new gene mutations and abnormalities in complex karyotypes of chromosomes.CONCLUSION Our findings suggest a possible molecular basis for the focal lymphoblastic transformation secondary to myeloblastic transformation in patients with CML.
文摘Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first-or second-line treatment in imatinib-resistant chronic myelogenous leukemia(CML)patients.Hepatotoxicity due to nilotinib is a commonly reported side effect;however,abnormal liver function test(LFT)results have been reported in asymptomatic cases.When alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels are more than five-fold the upper limit of the normal(ULN)or when the serum total bilirubin level is more than three-fold the ULN,dose modification or discontinuation of nilotinib is recommended,resulting in decreased levels of hematological indicators in certain patients with CML.Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels.Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver.The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity.Therefore,nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia,and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings,physicians should consider maintaining nilotinib dose intensity without modifications.
文摘970379 Risk of leukemia among diagnostic X-rayworkers in China between 1950 and 1990. WANG Juxi-an(王继先), et al. Radiat Med Instit, CAMS &PUMC, Tianjin, 300192. Chin J Hematol 1997; 18(2):84-86. Objective: To explore the relationship between radi-
