Roles of DNMT3B and PARP1 Genes Expression in Cytogenetically Normal Acute Myeloid Leukemia

Acute myeloid leukemia (AML) has a heterogeneous molecular profile, clinical presentations, and response to treatments and outcomes. DNA methylation is conducted by DNA methyltransferases including DNMT3B. Poly ADP-ribose polymerase 1 belongs to a family of enzymes that mediate important cellular processes including DNA repair, transcription, and cell death/cell proliferation, and it is involved in the development, spread, treatment, and prognosis of some cancers. The objective of this study is to assess the impact of PARP1 and DNMT3B genes expression on laboratory characteristics, response to treatment and survival in Egyptian cytogenetically normal AML patients.

This study included 67 Egyptian CN-AML patients in addition to 8 healthy bone marrow donors. Measurement of DNMT3B and PARP1 gene expression was done on bone marrow samples via real-time semiquantitative polymerase chain reaction.

Expression of both DNMT3B and PARP1 genes was significantly upregulated in AML (P = .001, P = .036, respectively). Upregulated DNMT3B was associated with higher total leukocyte count (TLC), PB, and BM blast cell%. Also, upregulated PARP1 correlated with higher TLC, PB, and BM blast cell%. High expression of both DNMT3B and PARP1 correlated with greater frequencies of FLT3-ITD. High DNMT3B expression, and combined upregulation of both PARP1 and DNMT3B genes associated significantly with ELN stratification. But no correlation was found with response (CR), overall survival (OS), disease-free survival (DFS), or event-free survival (EFS).

Our findings highlight the importance of considering DNMT3B and PARP1 expression levels as potential prognostic biomarkers for progression and aggressiveness of CN-AML patients in AML. Assessing their expression levels could be an indicator to guide treatment decisions and potentially improve patient outcomes.