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Review
. 2024 Dec;103(12):4981-4988.
doi: 10.1007/s00277-024-05874-x. Epub 2024 Jul 6.

DNMT3A-R882: a mutation with many paradoxes

Pourya Arbab Jafari  1 , Ramin Bagheri  2 , Soroush Lavasani  3 , Sajad Goudarzi  4
Affiliations
Review

DNMT3A-R882: a mutation with many paradoxes

Pourya Arbab Jafari et al. Ann Hematol. 2024 Dec.

Abstract

Understanding the underlying mechanism of acute myeloid leukemia (AML) has led to the discovery of novel biomarkers to help predict, treat and monitor leukemia. DNA (cytosine-5)-methyltransferase 3 A (DNMT3A) is considered a prognostic and therapeutic epigenetic target in AML patients with a hotspot mutation of R882. R882 mutation is associated with impaired differentiation of Hematopoietic stem cells in the bone marrow and disease progression. The prevalence of R882 mutation varied in different ethnicities and countries, and similarly, its prognostic impact differed among numerous studies. Nevertheless, the co-occurrence of mutations in R882 with NPM1 and FLT3 has been reported more frequently and is associated with a worse prognosis. These studies also suggest diverse results regarding bone marrow transplantation response as a treatment, while chemoresistance is reached as a conclusive outcome These findings highlight the crucial need for an in-depth discussion on the significance of the R882 mutation in AML patients. Understanding its impact on leukemic transformation, prognosis, and treatment is vital for advancing clinical implications.

Keywords: AML; DNMT3A; Prognosis; R882 mutation.

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Conflict of interest statement

Declarations. Ethical approval: This project did not require ethics approval. Competing interests: The authors declare no competing interests.

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