Loss of TET2 with reduced genomic 5-hmC is associated with adverse-risk AML

被引：5

作者：

Pethusamy, Karthikeyan ^{[1
]}

Seethy, Ashikh ^{[1
]}

Dhar, Ruby ^{[1
]}

Karmakar, Abhibroto ^{[1
]}

Chaudhary, Shilpi ^{[2
]}

Bakhshi, Sameer ^{[2
]}

Kumar, Jayanth P. ^{[1
]}

Chopra, Anita ^{[2
]}

Chauhan, Shyam S. ^{[1
]}

Karmakar, Subhradip ^{[1
]}

机构：

[1] All India Inst Med Sci, Dept Biochem, Room 3020, New Delhi 110029, India

[2] All India Inst Med Sci, Dr BR Ambedkar Inst Rotary Canc Hosp, New Delhi, India

来源：

LEUKEMIA & LYMPHOMA | 2022年 / 63卷 / 14期

关键词：

Acute myeloid leukemia; TET2; DNMT; cancer epigenetics; DNA DEMETHYLATION; VITAMIN-C; 5-METHYLCYTOSINE; MUTATIONS; DNMT3A; 5-HYDROXYMETHYLCYTOSINE; EXPRESSION; DIFFERENTIATION; CONVERSION; PROGNOSIS;

D O I：

10.1080/10428194.2022.2126278

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

While considerable information exists on the ten-eleven translocation 2 (TET2) mutational landscape in AML, the information on TET2 expression is limiting. So, we aimed to study the TET2 expression at mRNA and protein levels in AML patients compared to healthy controls. To achieve this, we recruited 70 non-M3, de novo AML patients and 20 healthy controls. The expression of TET2 was checked at mRNA and protein levels by qPCR and ELISA respectively and the TET activity was checked by the 5-hmC assay. TET2 mRNA expression was correlated with clinicopathological parameters and overall survival. We found a significant downregulation of TET2 mRNA and protein and significantly lower DNA 5-hmC levels in AML patients compared to controls. TET2 downregulation was more in patients with high blast counts and patients of the adverse-risk ELN category. We also found a significant upregulation of DNMT1 and DNMT3a suggesting a hypermethylation phenotype in de novo AML.

引用

页码：3426 / 3432

页数：7

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