Prognostic significance of Tet methylcytosine dioxygenase 2 (TET2) gene mutations in adult patients with acute myeloid leukemia: a meta-analysis

Abstract Mutations in the isocitrate dehydrogenase gene (IDH1) were recently described in patients with acute myeloid leukemia (AML). To investigate their prognostic significance we determined IDH1 status in 1333 young adult patients, excluding acute promyelocytic leukemia, treated in the United Kingdom MRC AML10 and 12 trials. A mutation was detected in 107 patients (8%). Most IDH1+ patients (91%) had intermediate-risk cytogenetics. Mutations correlated significantly with an NPM1 mutation (P < .0001) but not a FLT3/ITD (P = .9). No difference in outcome between IDH1+ and IDH1− patients was found in univariate or multivariate analysis, or if the results were stratified by NPM1 mutation status. However, when stratified by FLT3/ITD status, an IDH1 mutation was an independent adverse factor for relapse in FLT3/ITD− patients (P = .008) and a favorable factor in FLT3/ITD+ patients (P = .02). These results suggest that metabolic changes induced by an IDH1 mutation may influence chemoresistance in a manner that is context-dependent.

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Prognostic significance of the EVI1 gene expression in patients with acute myeloid leukemia: a meta-analysis

Annals of Hematology ◽

10.1007/s00277-019-03774-z ◽

2019 ◽

Vol 98 (11) ◽

pp. 2485-2496 ◽

Cited By ~ 2

Author(s):

Xia Wu ◽

Huifang Wang ◽

Jili Deng ◽

Xue Zheng ◽

Yantao Ling ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Meta Analysis ◽

Prognostic Significance ◽

Acute Myeloid

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Chromosome Aberrations, Gene Mutations and Expression Changes, and Prognosis in Adult Acute Myeloid Leukemia

Hematology ◽

10.1182/asheducation-2006.1.169 ◽

2006 ◽

Vol 2006 (1) ◽

pp. 169-177 ◽

Cited By ~ 75

Author(s):

Krzysztof Mrózek ◽

Clara D. Bloomfield

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Chromosome Aberrations ◽

Myeloid Leukemia ◽

Molecular Genetic ◽

Prognostic Significance ◽

Gene Mutations ◽

Normal Karyotype ◽

Genetic Alterations ◽

Acute Myeloid

Abstract Pretreatment clinical features and prognosis of patients with acute myeloid leukemia (AML) are strongly influenced by acquired genetic alterations in leukemic cells, which include microscopically detectable chromosome aberrations and, increasingly, submicroscopic gene mutations and changes in gene expression. Cytogenetic findings separate AML patients into three broad prognostic categories: favorable, intermediate and adverse. The cytogenetic-risk classifications differ somewhat for younger adult patients and those aged 60 years or older. In many instances, patients with specific cytogenetic findings, e.g., those with a normal karyotype or those with either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) [collectively referred to as core-binding factor (CBF) AML] can be further subdivided into prognostic categories based on the presence or absence of particular gene mutations or changes in gene expression. Importantly, many of these molecular genetic alterations constitute potential targets for risk-adapted therapies. In this article, we briefly review major cytogenetic prognostic categories and discuss molecular genetic findings of prognostic significance in two of the largest cytogenetic groups of patients with AML, namely AML with a normal karyotype and CBF AML.

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