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.
Humans ; Middle Aged ; Blast Crisis/drug therapy* ; Homoharringtonine/therapeutic use* ; Decitabine/therapeutic use* ; Interferons/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Treatment Outcome

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.
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*

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.
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*

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

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.
Adult ; Aged ; Blast Crisis ; Chromosome Aberrations ; Fusion Proteins, bcr-abl ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Middle Aged ; Retrospective Studies ; Young Adult

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.
Blast Crisis ; DNA Methylation ; Down-Regulation ; Fusion Proteins, bcr-abl ; Gelsolin ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Promoter Regions, Genetic

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.
Blast Crisis ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Clonal Evolution ; Disease Progression ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

OBJECTIVETo explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC).

METHODSBone 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).

RESULTSDeletions 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.

CONCLUSIONThe idic(Ph) chromosomes presented in CML-BLC may predict resistance to Imatinib and response to Dasatinib.

Blast Crisis ; diagnosis ; genetics ; therapy ; Chromosome Aberrations ; Chromosome Banding ; Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 9 ; genetics ; DNA Copy Number Variations ; Fatal Outcome ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; therapy ; Male ; Middle Aged ; Philadelphia Chromosome

No abstract available.
Blast Crisis* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Megakaryocyte Progenitor Cells*

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.
Blast Crisis ; genetics ; Disease Progression ; Epigenesis, Genetic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics