TET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia

Cui, Yajuan; Tong, Hongyan; Du, Xin; Li, Bing; Gale, Robert Peter; Qin, Tiejun; Liu, Jinqin; Xu, Zefeng; Zhang, Yue; Huang, Gang; Jin, Jie; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Xiao, Zhijian

doi:10.21037/sci.2016.09.04

Cited by 11 publications

(5 citation statements)

References 15 publications

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“…And the mutant mice developed phenotypes recapitulating human low-risk MDS and some of the mice developed MDS/myeloproliferative neoplasmlike disease after long latency (Uni et al, 2019). Consistent with the clinical prognosis (Cui et al, 2015(Cui et al, , 2016, hematopoieticspecific deletion of both Asxl1 and Tet2 leads to a much earlier onset of MDS than the deletion of Asxl1 or Tet2 alone. In support, Asxl1 deficiency accompanied with haploinsufficiency of Nf1 or KRas oncogenic mutation accelerates the development of myeloid leukemia in mice (Abdel-Wahab et al, 2012;Zhang et al, 2018).…”

Section: Asxl1 Mutations In Myeloid Malignancies: Loss or Gain-of-funmentioning

confidence: 70%

“…And the presence of the mutations is associated with adverse outcomes ( Gelsi-Boyer et al, 2009 , 2010 ; Boultwood et al, 2010 ; Chou et al, 2010 ; Metzeler et al, 2011 ; Thol et al, 2011 ; Itzykson et al, 2013 ). In CMML patients, additional TET2 mutations were associated with shorter survival in the presence of ASXL1 mutations ( Cui et al, 2015 , 2016 ). In contrast, ASXL1 mutations are mutually exclusive with DNMT3A , NPM1 , and SF3B1 mutations ( Asada et al, 2019 ).…”

Section: Asxl1 Mutations In Myeloid Malignancies: Loss or Gamentioning

confidence: 99%

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The Functions and Mechanisms of PR-DUB in Malignancy

Cao

2021

Front. Mol. Biosci.

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The interplay between cancer genome and deregulated epigenomic control is critical for cancer initiation and progression. ASXL1 (Additional Sex combs-like 1) is frequently mutated in tumors especially myeloid malignancies. However, there remains a debate whether the mutations are loss or gain-of-function. Mechanistically, ASXL1 forms a complex with BAP1 for the erasure of mono-ubiquitylation at lysine 119 on Histone H2A (H2AK119ub1), a well-known histone mark associated with transcription repression. Unexpectedly, this de-ubiquitylation complex has been genetically defined as a Polycomb Repressive complex though the regulatory mechanisms are elusive. In this review, we will discuss about the functions of ASXL1 in malignancies and reconcile seemingly paradoxical effects of ASXL1 or BAP1 loss on transcription regulation.

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Section: Asxl1 Mutations In Myeloid Malignancies: Loss or Gain-of-funmentioning

confidence: 70%

Section: Asxl1 Mutations In Myeloid Malignancies: Loss or Gamentioning

confidence: 99%

The Functions and Mechanisms of PR-DUB in Malignancy

Cao

2021

Front. Mol. Biosci.

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“…According to CMML epidemiological statistics, almost 90% of cases occur in patients older than 60 years 4,35,50 . We reviewed the literatures on the age of CMML patients in Western (Germany, 29,30,51 France, 13,19,52 America, 8,11,12,15,17,20,25,26,28,40,53,54 Italy, 39,55 Greece, 14 and Denmark, 24 ) and Eastern countries (Japan 16,22,27 and China, 6,43,49,56–63 ), and the results showed that the median age of CMML patients in Eastern countries was younger (38–70 years vs. 44–73 years), and the median age of CMML patients undergoing allo‐HSCT was similar in Eastern and Western countries (38–63 years vs. 44–64 years). However, the age of CMML patients undergoing allo‐HSCT was lower in both Eastern and Western countries.…”

Section: Discussionmentioning

confidence: 99%

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

Zhou,

Wang,

Yuan

et al. 2023

American J Hematol

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post‐transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0–1), intermediate risk (2, 3), and high risk (4–6) three groups and the 3‐year overall survival (OS) were 93.3% (95%CI, 61%–99%), 78.9% (95%CI, 60%–90%), and 51.6% (95%CI, 32%–68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776–0.902) and 0.749 (95% CI, 0.684–0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo‐HSCT.

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“…TET2 gene in this region is a tumor-suppressor gene 19 . The deletion or mutation of TET2 often predict inferior prognosis in patients with chronic myelomonocytic leukemia 20 . Although aberration in chromosome 5 has been considered as the most prevalent chromosomal lesion in MDS, some cryptic defects which affect additional key genes have not been clarified comprehensively.…”

Section: Discussionmentioning

confidence: 99%

Identify latent chromosomal aberrations relevant to myelodysplastic syndromes

Song

Chu

Yao

et al. 2017

Sci Rep

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Myelodysplastic syndromes (MDS) are a group of heterogeneous hematologic malignancies. This study aims to identify latent chromosomal abnormalities relevant to MDS, which may optimize the current diagnosis of MDS. Affymetrix CytoScan 750 K microarray platform was utilized to perform a genome-wide detection of chromosomal aberrations in the bone marrow cells of the patients. The findings were compared with the results from traditional karyotypic analysis and FISH to reveal latent chromosomal aberrations. Chromosomal gain, loss, and UPD, and complex karyotypes were identified in those samples. In addition to established cytogenetic aberrations detected by karyotypic analysis, CytoScan 750 K microarray also detected cryptic chromosomal lesions in MDS. Those latent defects underlying multiple gene mutations may construe the clinical variability of MDS. In Conclusion, Affymetrix CytoScan 750 K microarray is efficient in identifying latent chromosomal aberrations in MDS.

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TET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia

Cited by 11 publications

References 15 publications

The Functions and Mechanisms of PR-DUB in Malignancy

The Functions and Mechanisms of PR-DUB in Malignancy

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

Identify latent chromosomal aberrations relevant to myelodysplastic syndromes

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