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Study of DNA methyl transferase 3A mutation in acute myeloid leukemic patients

Ghada M. Elsayed
Abd Elgawad A. Fahmi
Nevine F. Shafik
Reham A.A. Elshimy
Heba K. Abd Elhakeem
Sara A. Attea


Background: Recent studies have shown that somatic mutations in DNA methyltransferase (DNMT3A) might affect the prognosis of AML.

Objective: The aim of this work was to investigate the frequency and prognostic impact of the most frequent mutation of DNMT3A, R882H mutation in AML using simple and rapid molecular techniques.

Patients and methods: We have used allele-specific blocker (ASB-PCR) and endonuclease restriction for the detection of DNMT3A R882H mutation in 56 adult patients with AML.

Results: DNMT3A R882H mutation was detected in 7/56 (12.5%) of patients. R882H mutation positive patients were older compared to the wild-type AML (p = 0.08). No association was found with initial laboratory parameters including white blood cells (WBC), hemoglobin (HGB) and Bone marrow (BM) blasts (p > 0.05). Thirty-two patients (57.1%) achieved complete remission (CR), 11/56 (19.6%) died before day 28 induction death (ID) and 13/56 (23.2%) had resistant disease (RD). DNMT3A R882H positive patients were not different regarding the response to induction chemotherapy (CR) compared to the negative group (wild-type) (p > 0.05). Median follow-up period for all patients was 1.6 months, Overall survival (OS) was 65%, and the median was 9.89 months. OS of DNMT3A positive patients was not statistically significant compared to wild-type patients (p = 0.09). Disease free survival (DFS) was 54.6% for all patients, with no difference between wild and mutants (0.59) patients.

Conclusion: DNMT3A R882H is a frequent mutation in adult de novo AML. The frequency of the mutation tends to increase with age. The two methods used in the study are easy to interpret and are recommended for rapid detection of the mutation required for risk stratification.

Keywords: AML, DNMT3A, ASB-PCR, PCR-RFLP, Endonuclease restriction