Emergence of clone with PHF6 nonsense mutation in chronic myelomonocytic leukemia at relapse after allogeneic HCT

2022 ◽  
Author(s):  
Yu Akahoshi ◽  
Hideki Nakasone ◽  
Machiko Kusuda ◽  
Kazuaki Kameda ◽  
Yuhei Nakamura ◽  
...  
Keyword(s):  
Nonsense Mutation ◽  
Chronic Myelomonocytic Leukemia ◽  
Allogeneic Hct ◽  
Myelomonocytic Leukemia

Management of Patients After the Failure of Hypomethylating Treatment for Myelodysplastic Syndrome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4953-4953
Author(s):  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Yunsuk Choi ◽  
Dae-Young Kim ◽  
Kyoo-Hyung Lee ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Treatment Failure ◽  
Salvage Therapy ◽  
Disease Status ◽  
Chronic Myelomonocytic Leukemia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Term Survival ◽  
Allogeneic Hct ◽  
Myelomonocytic Leukemia

Abstract Abstract 4953 Introduction: Although treatment with hypomethylating agents such as azacitidine or decitabine has been the standard of care for patient with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), about half of the patients fail to respond to the agents and most responders progress within 2 years. Retrospective studies showed poor outcomes after failure of treatment with azacitidine or decitabine and there is no standard salvage therapy for patients who fail hypomethylating treatment (HMT). We retrospectively studied outcomes of patients who failed HMT and analyzed the effects of salvage therapy after HMT failure. Methods: Between September 2006 and October 2010, a total of 149 patients were treated with either azacitidine (n=75) or decitabine (n=74) for MDS defined by the WHO classification and chronic myelomonocytic leukemia (CMML) in 3 Korean institutes. Ninety-one of the 149 patients were included in this study and disease status at the end of HMT was categorized as stable disease (n=22), primary progression (n=17), progression after response (n=38), and intolerance (n=14). Six patients who were still receiving hypomethylating agents with a median of 19 courses (range, 15 to 48) and 52 patients who stopped hypomethylating agents for other reasons were excluded from the analysis. Results: Median age was 59 years (range, 23 to 80) at the time of HMT failure. Median follow-up duration of surviving patients was 47. 8 months (range, 5. 8 to 62. 9) and 69 patients died. Probability of overall survival (OS) at 3 years was 28. 1% and median OS was 12. 1 months (95% confidence interval [CI], 9. 8 to 14. 4). Multivariate analysis showed that disease status and evolution to acute myeloid leukemia (AML) at HMT failure were independent prognostic factors for OS. A total of 37 patients (40. 7%) received supportive care only after HMT failure and other patients were managed with one or more treatments including immunosuppressive therapy (n=7), low-dose cytarabine (n=9), androgen (n=8), alternate azanucleoside (n=2), intensive chemotherapy (n=24), and allogeneic hematopoietic cell transplantation (HCT) (n=23). Objective response to non-transplant treatment was observed in 11–17% of evaluable patients, while 17 (74%) of 23 patients who received allogeneic HCT attained complete response. Probability of OS at 2 years (from HCT) was 60. 9% in the transplanted patients; it was 78. 6% in patients who received HCT during MDS and 33. 3% in those who received HCT after AML evolution (P=0. 016). Conclusions: The clinical outcomes of patients after hypomethylating treatment failure are poor; especially, AML evolution at the time of hypomethylating treatment failure and primary progression after hypomethylating treatment indicated very poor prognosis. Responses to various low intensity therapies and intensive chemotherapy were infrequent. Long-term survival without disease evidence was observed in about half of the patients who received allogeneic HCT. In appropriately selected patients, allogeneic HCT should be performed in earlier period, especially before evolution to AML. Patients with MDS that has failed to respond to hypomethylating agents should be referred for clinical trials when available. Disclosures: No relevant conflicts of interest to declare.

Off-pump Coronary Artery Bypass Grafting in a Patient with Chronic Myelomonocytic Leukemia

2003 ◽  
Vol 44 (3) ◽  
pp. 435-439 ◽  
Author(s):  
Kazuhiro Ito ◽  
Hideyuki Kawachi ◽  
Katsuhiko Nishiyama ◽  
Hitoshi Yaku ◽  
Nobuo Kitamura
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Bypass Grafting ◽  
Coronary Artery Bypass ◽  
Artery Bypass ◽  
Chronic Myelomonocytic Leukemia ◽  
Bypass Grafting ◽  
Artery Bypass Grafting ◽  
Off Pump ◽  
Pump Coronary Artery Bypass ◽  
Myelomonocytic Leukemia

scholarly journals Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study

2020 ◽  
Vol 50 (5) ◽  
pp. 879-884
Author(s):  
Anne Laure Roupie ◽  
Alexis Guedon ◽  
Benjamin Terrier ◽  
Constance Lahuna ◽  
Vincent Jachiet ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Case Control Study ◽  
Case Control ◽  
Chronic Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia ◽  
Control Study

Trisomy 19 as the sole chromosomal abnormality in proliferative chronic myelomonocytic leukemia

2006 ◽  
Vol 30 (8) ◽  
pp. 1043-1047 ◽  
Author(s):  
M. Daskalakis ◽  
N. Mauritzson ◽  
B. Johansson ◽  
K. Bouabdallah ◽  
F. Onida ◽  
...  
Keyword(s):  
Chromosomal Abnormality ◽  
Chronic Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia

scholarly journals Asxl1 C-terminal mutation perturbs neutrophil differentiation in zebrafish

Leukemia ◽  
2021 ◽  
Author(s):  
Xiao Fang ◽  
Song’en Xu ◽  
Yiyue Zhang ◽  
Jin Xu ◽  
Zhibin Huang ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Chronic Myelomonocytic Leukemia ◽  
Nonsense Mutations ◽  
Myeloid Malignancies ◽  
A Subunit ◽  
Neutrophil Differentiation ◽  
Polycomb Repressive Complex 1 ◽  
Myelomonocytic Leukemia ◽  
Inhibitor Treatment ◽  
Acute Myeloid

AbstractASXL1 is one of the most frequently mutated genes in malignant myeloid diseases. In patients with myeloid malignancies, ASXL1 mutations are usually heterozygous frameshift or nonsense mutations leading to C-terminal truncation. Current disease models have predominantly total loss of ASXL1 or overexpressed C-terminal truncations. These models cannot fully recapitulate leukemogenesis and disease progression. We generated an endogenous C-terminal-truncated Asxl1 mutant in zebrafish that mimics human myeloid malignancies. At the embryonic stage, neutrophil differentiation was explicitly blocked. At 6 months, mutants initially exhibited a myelodysplastic syndrome-like phenotype with neutrophilic dysplasia. At 1 year, about 13% of mutants further acquired the phenotype of monocytosis, which mimics chronic myelomonocytic leukemia, or increased progenitors, which mimics acute myeloid leukemia. These features are comparable to myeloid malignancy progression in humans. Furthermore, transcriptome analysis, inhibitor treatment, and rescue assays indicated that asxl1-induced neutrophilic dysplasia was associated with reduced expression of bmi1a, a subunit of polycomb repressive complex 1 and a reported myeloid leukemia-associated gene. Our model demonstrated that neutrophilic dysplasia caused by asxl1 mutation is a foundation for the progression of myeloid malignancies, and illustrated a possible effect of the Asxl1-Bmi1a axis on regulating neutrophil development.

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