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DNMT3A-R882: a mutation with many paradoxes

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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.

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Data availability

No datasets were generated or analysed during the current study.

Notes

  1. Regions of DNA which is enriched in Cytosines and Guanines bases.

  2. a CD-CD homodimeric interface.

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Authors and Affiliations

  1. Deakin University, Melbourne, Australia

    Pourya Arbab Jafari

  2. Mashhad University of Medical Sciences, Mashhad, Iran

    Ramin Bagheri & Sajad Goudarzi

  3. Iran University of Medical Sciences, Tehran, Iran

    Soroush Lavasani

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  1. Pourya Arbab Jafari
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  2. Ramin Bagheri
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  3. Soroush Lavasani
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  4. Sajad Goudarzi
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Contributions

Pouriya Arbab Jafari conceived the idea. Pouriya Arbab Jafari and Ramin Bagheri wrote the draft. Soroush Lavasani draw the table and gathered its Data. Sajad Goudarzi supervised and revised the manuscript.

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Correspondence to Sajad Goudarzi.

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Jafari, P.A., Bagheri, R., Lavasani, S. et al. DNMT3A-R882: a mutation with many paradoxes. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05874-x

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