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1.
Chinese Journal of Hematology ; (12): 276-283, 2023.
Article in Chinese | WPRIM | ID: wpr-984615

ABSTRACT

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.


Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Blast Crisis/drug therapy , Primary Myelofibrosis/genetics , Prognosis , Splenomegaly , Retrospective Studies , Myeloproliferative Disorders/genetics , Mutation , Leukemia, Myeloid, Acute , Janus Kinase 2/genetics
2.
Article in Chinese | WPRIM | ID: wpr-982111

ABSTRACT

OBJECTIVE@#To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP).@*METHODS@#The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test.@*RESULTS@#A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR=0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR=0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR=0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group.@*CONCLUSION@#The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.


Subject(s)
Humans , Middle Aged , Blast Crisis/drug therapy , Homoharringtonine/therapeutic use , Decitabine/therapeutic use , Interferons/therapeutic use , Inhibitors, Tyrosine Kinase , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Treatment Outcome
3.
Article in Chinese | WPRIM | ID: wpr-982114

ABSTRACT

OBJECTIVE@#To investigate the expression and significance of regulatory T cells (Tregs), FoxP3 and transforming growth factor-β (TGF-β) in different phase of chronic myeloid leukemia (CML).@*METHODS@#Peripheral blood of 73 CML patients in Department of Hematology, Heze Municipal Hospital from March 2018 to March 2021 were collected. According to patient's period in CML, they were divided into ND CML group (newly diagnosed), CP CML group (chronic period), and BP CML group (blast phase). The percentage of Tregs, expression level of FoxP3 mRNA and TGF-β were detected by flow cytometry, RT-qPCR, and ELISA, respecitively. The roles of above indices in clinical pathogenesis of patients with CML were analyzed.@*RESULTS@#The proportion of Treg in the ND CML group was slightly higher than the CP CML group, but the difference was not statistically significant (P =0.695), while the BP CML group was significantly higher than the other two groups (P =0.008, P <0.001). The expression levels of FoxP3 mRNA in ND CML group, CP CML group and BP CML group were 11.61±2.21, 6.46±1.35 and 8.54±2.13, respectively. Significant difference in FoxP3 mRNA levels was observed among patients in different phases of CML (F =55.199, P <0.001). The expression levels of FoxP3 mRNA both in ND CML group and BP CML group were significantly higher than that in CP CML group (P <0.001), and the ND CML group was the highest (P <0.001). However, the expression levels of TGF-β in different phases of CML showed no statistical differences (H =0.634, P =0.728).@*CONCLUSION@#The abnormal distribution of Treg subset in different phases of CML and the significant increase of the expression level of FoxP3 mRNA in the new onset and blast phase of CML suggest that Tregs may promote the occurrence and progression of CML through immune regulation.


Subject(s)
Humans , Blast Crisis/metabolism , Forkhead Transcription Factors/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , RNA, Messenger/metabolism , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/metabolism
6.
Article in Chinese | WPRIM | ID: wpr-771849

ABSTRACT

OBJECTIVE@#To retrospectively analyze the clinical manifestation, laboratorial test features and prognosis of patients with CML in myeloid blast crisis.@*METHODS@#The clinical data of 10 patients with CML in myeloid blast crisis admitted in Chinese PLA General Hospital from June 2011 to May 2018 were collected, and their clinical features, laboratorial data and long-term survival were analyzed.@*RESULTS@#The median age of these 10 cases was 32.5 (23-73) years old. Nine cases had chronic phase history. The median chronic phase was 17(4-84) months. All the 10 cases had splenomegaly; B-ultrasonography showed that the median spleen size was 5.2 (4-7.8) cm in thickness, and 14.6 (11.4-19.8) in length. When chronic myeloid leukemia was in blast crisis, the median WBC count was 41.705(11.9-344.41)×10 /L and the median platelet count was 159 (13-2326) ×10 /L. The Ph+ chromosome and BCR-ABL1 fusion gene coulld be detected in all the cases. The chromosome karyotyping showed that additional chromosome abnormalities were found in 5 cases. One case was of low diploid, and two cases were with complex karyotype. ABL1 mutation was detected in 6 out of these 10 cases. ABL1 T315I mutation was detected in 2 of them and one was with deletion of combined P53 in genetic tests. The median follow-up time was 10.5(0.2-78) months. There were 5 cases treated sequentially by chemotheraphy with or without TKI and allo-HSCT. Three cases reached CP2 before transplantation. Among them, two cases still survived without progression for 67 months and 69 months after the transplantation respectively. One case died of transplantation-related mortality (suffered from cerebral hemorrhage 7 months after the transplantation). Two cases were NR before the transplantation, and both died of disease relapse or progression at the time points of one or three months after the transplantation. Five cases treated by TKI ± chemotheraphy and without HSCT succumbed to disease progression. The median time was 6(0.2-22) months.@*CONCLUSION@#CML patients in myeloid blast crisis treated by chemotheraphy combined with TKI gain CP2, the survival time of patients treated by sequential allo-HSCT is prolonged.


Subject(s)
Adult , Aged , Humans , Middle Aged , Young Adult , Blast Crisis , Chromosome Aberrations , Fusion Proteins, bcr-abl , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Retrospective Studies
7.
Article in Chinese | WPRIM | ID: wpr-771904

ABSTRACT

OBJECTIVE@#To investigate the clinical significance of SCIN gene expression and promoter methylation in patients with chronic myeloid leukemia (CML).@*METHODS@#Real-time quantitative PCR was used to detect the expression level of SCIN in mononucleatr cells of bone marrow samples from 64 CML patients and 37 controls. The methylation levels of SCIN promoter in 65 patients with CML and 29 controls were detected by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR.@*RESULTS@#The expression level of SCIN in CML patients was significantly down-regulated (P<0.05), compared with the control group. The down-regulation rate of SCIN expression in CML patients at chronic phase, accelerated phase and blast crisis was 61%, 67% and 75%, respectively. Spearman correlation analysis showed that the expression level of SCIN negatively correlated with the transcript level of BCR-ABL1 (R=-0.315, P<0.05). However, there was no significant difference in clinical parameters such as sex, age, white blood cell count, hemoglobin level, platelet count, chromosome, CML staging and BCL-ABL1 transcript level between low and high SCIN expression groups of CML patients (P>0.05). No significant difference in methylation of SCIN promoter between CML patients and controls, and no correlation between SCIN expression and promoter methylation were observed (P>0.05).@*CONCLUSION@#The SCIN expression is down-regulated in CML patients, which may relate with the pathogenesis that is, BCR-ABL1 fusion gene induces CML tumorigenesis. The down-regulation of SCIN expression may relate with the progression of CML.


Subject(s)
Humans , Blast Crisis , DNA Methylation , Down-Regulation , Fusion Proteins, bcr-abl , Gelsolin , Genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Promoter Regions, Genetic
8.
Journal of Experimental Hematology ; (6): 1598-1603, 2018.
Article in Chinese | WPRIM | ID: wpr-773050

ABSTRACT

OBJECTIVES@#To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression.@*METHODS@#An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported.@*RESULTS@#This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period.@*CONCLUSION@#These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.


Subject(s)
Humans , Blast Crisis , Chromosome Aberrations , Chromosomes, Human, Pair 8 , Clonal Evolution , Disease Progression , Leukemia, Myelogenous, Chronic, BCR-ABL Positive
10.
Article in Chinese | WPRIM | ID: wpr-345318

ABSTRACT

<p><b>OBJECTIVE</b>To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC).</p><p><b>METHODS</b>Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH). Variations of acute lymphoblastic leukemia-related genes including CDKN2A/AB and PAX5 were detected by multiplex ligation-dependent probe amplication (MLPA).</p><p><b>RESULTS</b>Deletions and duplications on derivative chromosome 9 detected by FISH were confirmed by SNP array analysis. The distances between the BCR/ABL fusion signals on the idic(Ph) chromosomes in the two patients have differed greatly. The idic(Ph) in the second patient was supposed to be formed by two Ph chromosomes joined at their q terminals, where as the idic(Ph) in the first patient have been shown to be fused at the satellite regions of their p arms.</p><p><b>CONCLUSION</b>The idic(Ph) chromosomes presented in CML-BLC may predict resistance to Imatinib and response to Dasatinib.</p>


Subject(s)
Female , Humans , Male , Middle Aged , Blast Crisis , Diagnosis , Genetics , Therapeutics , Chromosome Aberrations , Chromosome Banding , Chromosome Deletion , Chromosome Duplication , Chromosomes, Human, Pair 9 , Genetics , DNA Copy Number Variations , Fatal Outcome , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Diagnosis , Genetics , Therapeutics , Philadelphia Chromosome
12.
Journal of Experimental Hematology ; (6): 1039-1043, 2016.
Article in Chinese | WPRIM | ID: wpr-246820

ABSTRACT

<p><b>OBJECTIVE</b>To compare the efficacy and drug resistance of imatinib in patients with chronic myeloid leukemia (CML) at chronic phase (CP) and advanced phase (accelerated phase and blast crisis (AP+BC).</p><p><b>METHODS</b>Forty-two patients with CML were treated with imatinib of different doses(CP 400 mg/d, AP+BC 600 mg/d), and the efficacy and drug resistance of the 2 groups were compared. The median follow-up time was 24 months (3-42 months).</p><p><b>RESULTS</b>The complete hematological remission rate (CHR), the major cytogenetic remission rate (MCyR) and complete molecular remission rate (CMoR) in the CP group were 100%, 89.6% and 20.1% respectively, while those in advanced phase group were 46.2%, 308% and 0; survival rate of 42 months in CP patients was 76.7%, and that in advanced phase group was 39.2%, the difference between them was statistically significant (P<0.05). The incidence of severe hematologic adverse reaction in advanced phase group was higher than that in CP Group; among 42 cases of CML, the drug-resistance happened in 13 cases, out of them 9 cases was CML in advanced phase; the drug resistance rate in CML in advanced phase group (69.2%) was significantly higher than that in CML-CP group(13.8%). The correlation factor analysis showed that the effects of the advanced phase and the lower dose of the drug were statistically significant.</p><p><b>CONCLUSION</b>Imatinib can provide certain curative effect for CML patients at different phases, especially for the patients at chronic phase; the early MCyR for patients with CML is an important factor in long-term survival; drug resistance is an important factor affecting the efficacy of imatinib; The incidence of imatinib drug resistance at the late stage has been found to be higher.</p>


Subject(s)
Humans , Antineoplastic Agents , Blast Crisis , Cytogenetics , Drug Resistance, Neoplasm , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Remission Induction , Survival Rate
13.
Chinese Journal of Hematology ; (12): 110-114, 2016.
Article in Chinese | WPRIM | ID: wpr-234021

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).</p><p><b>METHODS</b>The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing.</p><p><b>RESULTS</b>In 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months.</p><p><b>CONCLUSION</b>T315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.</p>


Subject(s)
Humans , Acute Disease , Blast Crisis , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl , Genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Drug Therapy , Genetics , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Drug Therapy , Genetics , Protein Kinase Inhibitors , Therapeutic Uses
14.
Article in Chinese | WPRIM | ID: wpr-234042

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficiency of dasatinib as the second- or third-line tyrosine kinase inhibitor (TKI)in imatinib-resistant patients with chronic myeloid leukemia (CML)based on BCR-ABL mutation detection.</p><p><b>METHODS</b>122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib- and nilotinib-resistance, 55 in the chronic-phase (CP), 21 in the accelerated- phase (AP)and 46 in the blast- phase (BP). Those harboring dasatinib highly- resistant mutations (T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival (PFS)and overall survival (OS)were analyzed. BCR- ABL mutation detection was performed once the patients failed on dasatinib.</p><p><b>RESULTS</b>In the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR)and molecular response 4.5 (MR4.5)were 92.7%, 53.7%, 29.6% and 14.8%, respectively. 4-year PFS and OS rates were 84.4% and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0% and 35.0%; and 3-year PFS and OS rates were 56.1% and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0% and 21.4%; and 1-year PFS and OS rates were 43.6% and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second- line TKI or the third-line TKI. Of the 75 patients who were resistant to dasatinib, 37 (48.7%)developed new mutation(s), and T315I (59.5%)was the most common mutation type. The patients who already harbored mutation(s)before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib (65.7%vs 34.1%,P=0.006).</p><p><b>CONCLUSIONS</b>Dasatinib was proved to be effective in the treatment of imatinib- or/and nilotinib-resistant CML patients, especially in both CP and AP cohorts. The significance of BCR-ABL mutation screening and monitoring should be highlighted before and during dasatinib therapy.</p>


Subject(s)
Humans , Blast Crisis , Cytogenetics , Dasatinib , Therapeutic Uses , Disease-Free Survival , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl , Metabolism , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Drug Therapy , Mutation , Protein Kinase Inhibitors , Therapeutic Uses , Pyrimidines
15.
Article in Chinese | WPRIM | ID: wpr-360107

ABSTRACT

Chronic myeloid leukemia is a myeloproliferative disorder characterized by excessive cloning of bone marrow multipotent stem cells. According to the disease course, the CML may be divided into chronic phase (CP), accelerated phase (AP) and blastic phase (BP). At present, the molecular mechanisms of acute transformation of CML has not been fully understood. The recent studies have shown that the epigenetics is one of mechanisms in blastic transformation of CML, including three molecular mechanisms such as DNA modification, histone modifications and RNA-related dysregulation. The molecular mechanisms for epigenetics leading to the transformation of CML are discussed in this review.


Subject(s)
Humans , Blast Crisis , Genetics , Disease Progression , Epigenesis, Genetic , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics
16.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;48(6): 509-514, 06/2015. tab, graf
Article in English | LILACS | ID: lil-748223

ABSTRACT

We measured circulating endothelial precursor cells (EPCs), activated circulating endothelial cells (aCECs), and mature circulating endothelial cells (mCECs) using four-color multiparametric flow cytometry in the peripheral blood of 84 chronic myeloid leukemia (CML) patients and 65 healthy controls; and vascular endothelial growth factor (VEGF) by quantitative real-time PCR in 50 CML patients and 32 healthy controls. Because of an increase in mCECs, the median percentage of CECs in CML blast crisis (0.0146%) was significantly higher than in healthy subjects (0.0059%, P<0.01) and in the accelerated phase (0.0059%, P=0.01). There were no significant differences in the percentages of CECs in chronic- or active-phase patients and healthy subjects (P>0.05). In addition, VEGF gene expression was significantly higher in all phases of CML: 0.245 in blast crisis, 0.320 in the active phase, and 0.330 in chronic phase patients than it was in healthy subjects (0.145). In conclusion, CML in blast crisis had increased levels of CECs and VEGF gene expression, which may serve as markers of disease progression and may become targets for the management of CML.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Blast Crisis/pathology , Endothelial Cells/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Neoplastic Cells, Circulating/pathology , Vascular Endothelial Growth Factor A/genetics , Biomarkers, Tumor/analysis , Blast Crisis/blood , Blast Crisis/genetics , Case-Control Studies , Cell Count , Flow Cytometry/methods , Gene Expression/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Neovascularization, Pathologic/pathology , Real-Time Polymerase Chain Reaction , Reference Values , Statistics, Nonparametric , Vascular Endothelial Growth Factor A/analysis
17.
Rev. cuba. hematol. inmunol. hemoter ; 31(1): 71-78, ene.-mar. 2015.
Article in Spanish | LILACS | ID: lil-743986

ABSTRACT

La leucemia mieloide crónica es una neoplasia mieloproliferativa de naturaleza clonal que generalmente y de manera progresiva transita por tres fases: crónica, acelerada y crisis blástica. Alrededor del 80 por ciento de los enfermos con leucemia mieloide crónica son diagnosticados durante la fase crónica, 10 por ciento en fase acelerada y otro 10 por ciento durante la crisis blástica. A la presencia del cromosoma Filadelfia y la formación del gen de fusión BCR/ABL, que se traduce en la proteína quimérica pBCR/ABL, le sigue una gran inestabilidad genómica y la adquisición de alteraciones cromosómicas y moleculares adicionales. Algunas alteraciones moleculares, que suelen estar presentes en otras hemopatías malignas, pueden ser adquiridas durante la progresión de la leucemia mieloide crónica a crisis blástica. Se presenta el caso de un paciente que debutó con una leucemia mieloide crónica en crisis blástica, con positividad del gen de fusión BCR/ABL, el gen de fusión AML-1/ETO y la mutación NPM-1A(AU)


Chronic myeloid leukemia is a clonal myeloproliferative neoplasm which generally and progressively goes through three phases: chronic, accelerated and blast crisis. About 80 percent of patients with chronic myeloid leukemia are diagnosed in chronic phase, 10 % in accelerated phase and 10 percent in blast crisis. The presence of Philadelphia chromosome and the formation of BCR/ABL fusion gene, resulting in the chimeric protein pBCR/ABL, generates a large genomic instability and the acquisition of additional chromosomal and molecular alterations. Some molecular alterations, which are usually present in other hematological malignancies, could be acquired during the progression of chronic myeloid leukemia to blast crisis. This report presents the case of a patient with de novo chronic myeloid leukemia in blast crisis, with positivity of BCR/ABL fusion gene, AML-1/ETO fusion gene and mutation NPM-1A(AU)


Subject(s)
Humans , Male , Aged , Blast Crisis/diagnosis , Leukemia, Megakaryoblastic, Acute/diagnosis , Chromosome Aberrations
18.
Journal of Experimental Hematology ; (6): 1199-1202, 2015.
Article in Chinese | WPRIM | ID: wpr-274066

ABSTRACT

Chronic myeloid leukemia (CML) is a myeloproliferative disorder, characterized by excessive proliferation of myeloid cells. CML patients in early phase [also known as chronic phase (CP)] usually respond to treatment with tyrosine kinase inhibitors (TKI), some patients respond initially to TKI, but later become resistant, then resulting in the transformation from CP to more advanced phase, which were subclassified as either accelerated phase or blastic phase. At present, the molecular mechanisms of CML have been not yet clear, and acute transformation has been not fully understood, studies have shown that genomic instability promotes the acute conversion of CML. This review discusses the molecular mechanisms leading to the transformation of CML, and some therapeutic approaches.


Subject(s)
Humans , Blast Crisis , Drug Resistance, Neoplasm , Genomic Instability , Leukemia, Myelogenous, Chronic, BCR-ABL Positive
19.
Chinese Journal of Hematology ; (12): 398-402, 2015.
Article in Chinese | WPRIM | ID: wpr-282023

ABSTRACT

<p><b>OBJECTIVE</b>To explore the clinical and laboratory characteristics in favor of the diagnosis of Ph/BCR-ABL positive acute myeloid leukemia (Ph/BCR-ABL⁺ AML).</p><p><b>METHODS</b>Retrospectively analyzed the clinical and laboratory characteristics of 12 Ph/BCR-ABL⁺ AML cases from Feb, 2006 to Dec, 2013, with classic myeloid blast crisis of chronic myeloid leukemia (CML-MBC) as control, and followed-up the survival in these two cohorts of patients.</p><p><b>RESULTS</b>The median age of 12 Ph/BCR-ABL⁺ AML was 27.5 years, 10 cases (83.3%) showed non/mild splenomegaly, and mainly comprised of M₂ and M₄ subtypes according to FAB classification. The median number of basophils and megakaryocytes in peripheral blood and bone marrow was lower than that of CML-CBC patients. All the cases expressed myeloid antigens, 8 cases (66.7%) expressed CD34, 11 cases were detected with t(9;22), 5 cases (45.5%) with additional chromosomal abnormalities, including 1 case of inv(16). All the cases had BCR-ABL transcripts at diagnosis:3(25.0%) cases were e1a2 type and the remaining was b2a2/b3a2type, among which 1 case coexpressed CBFβ-MYH11. Two out of 6 cases existed AML-like mutations:1 case of CEBPA and the other of FLT3-TKD. For all the patients, 7 cases achieved complete remission (CR), including 6 out of 7 cases receiving induction chemotherapy combined with tyrosine kinase inhibitor (TKI) achieved CR, and 1 out of 3 cases receiving chemotherapy alone achieved CR. The median overall survival was 16.5 months, that of allo-HSCT group was 33.5 months, which was higher than that of non-HSCT group (5.5 months).</p><p><b>CONCLUSION</b>The expression of e1a2 type BCR-ABL, the coexpression of fusion genes which were more common in AML, the existence of AML-like mutations were all indications of a de novo Ph/BCR-ABL⁺ AML. Low induction CR rate and short survival of Ph/BCR-ABL⁺ AML implied that chemotherapy combined with TKI and followed by allo-HSCT in CR was the only effective way to improve their survival.</p>


Subject(s)
Adult , Humans , Blast Crisis , Chromosome Aberrations , Fusion Proteins, bcr-abl , Leukemia, Myeloid, Acute , Oncogene Proteins, Fusion , Protein Kinase Inhibitors , Retrospective Studies
20.
Article in Chinese | WPRIM | ID: wpr-259585

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate efficacy and safety of second-generation tyrosine kinase inhibitors (TKI) dasatinib, nilotinib and imatinib in treatment of newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML).</p><p><b>METHODS</b>The clinical data and follow-up results of 163 patients with chronic-phase chronic myeloid lenkemia(CP-CML) who were treated in our hospital during the nearly 3 years were analysed retrospectively, among 163 patients 47 received dasatinib, 43 received nilotinib and 73 received imatinib. The efficacy, disease progression and safety were evaluated.</p><p><b>RESULTS</b>After treatment for 3 months, the rate of complete hematologic response(CHR) in three treatment groups were 77%, 79% and 67%, respectivily, CHR at 12 months in three treatment groups were 92%, 91% and 90%, respectively. By 3 months, the rates of complete cytogenetic response(CCyR) with dasatinib and nilotinib were higher than that with imatinib (55%, 53% vs 33%)(P<0.05 for both comparisons), CCyR at 12 months in three treatment groups were 86%, 88% vs 69% (P<0.05 for both comparisons). The rates of major molecular response(MMR) for dasatinib (11%) and nilotinib (9%) by 3 months were significantly higher than that for imatinib (1%) (P<0.05 for both comparisons), MMR at 12 months in three treatment groups were 49%, 50% and 28%, respectively (P<0.05 for both comparison). Progression to the accelerated or blast phase of CML occurred in 2 (4%) patients received dasatinib, 2 (5%) received nilotinib and 6 (8%) received imatinib. The safety profiles of these 3 second-generation TKI treatments were similar.</p><p><b>CONCLUSION</b>Both dasatinib and nilotinib induced strikingly higher and faster rates of complete cytogenetic response and major molecular response, with a statistically significant difference from imatinib.</p>


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Blast Crisis , Dasatinib , Disease Progression , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Pyrimidines , Retrospective Studies , Treatment Outcome
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