Overall, remarkable association of reduced expression of BECN1 with FLT3-ITD mutation and monosomal karyotype and their functional relationship is interesting which should be addressed and verified in future studies.

In relation to DNMT3A expression, from the perspective of diagnostic application and its biological significance, it is difficult to accept its primacy over cytogenetic value in favorable and unfavorable subgroups and if so, we did not address this issue in our study due to sample size limitation. In intermediate subgroup, particularly in normal karyotype-AML, given the lack of convincing results, it seems unlikely that DNMT3A expression analysis could attract attention in diagnostic workup and risk prediction of AML.

In acute myeloid leukemia (AML), despite the acceptance of standard intensive chemotherapy as an optimal induction regimen for all age groups, in the elderly patients, the best treatment should meet the challenge of multiple factors like age, comorbidities, and cytogenetics, making them ineligible for standard induction chemotherapy. Using the current low-intensity therapies like decitabine, azacitidine, and low-dose cytarabine as a single arm, outcomes for these patients remain poor. As a histone deacetylase inhibitor valproic acid (VPA) exhibit anticancer activity by triggering apoptosis, the mechanism of which is not yet completely clarified. To explore the possible connection between VPA treatment and the Hippo pathway as an apoptosis stimulating route, we also explore the expression of major components of this pathway and for the first time we postulate a relationship between VPA treatment and cell death induction through RASSF1A expression induction. Furthermore, we demonstrate that autophagy inhibition by chloroquine (CQ) significantly augmented the cytotoxic effect of VPA on AML cells, especially in those with unfavorable and normal karyotype. Regarding that VPA and CQ are well-tolerated drugs and our presumptive results of usefulness of VPA + CQ in three cytogenetic risk groups of AML, this combinatorial therapy could represent an attractive treatment option for older AML patients unfit for intensive therapy.

As a typical tumor suppressor gene, transcriptional silencing of ras-association domain family 1, isoform A (RASSF1A) is caused by biallelic methylation or the condition that one allele is methylated and then the other allele lost by allelic loss, as second hit. RASSF1A is inactivated epigenetically and thus down-regulated in many solid tumors. In summary, for the first time, we analyzed the expression status of RASSF1A in a cohort of 56 de novo acute myeloid leukemia (AML) patients using quantitative real-time polymerase chain reaction. Results of our study indicate that patients with AML exhibited no differences in the RASSF1A gene expression comparing to normal controls. In conclusion, expression status of RASSF1A remained intact in our target samples, indicating that RASSF1A expression variation does not participate in the pathogenesis and the progression of AML.

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