Clinical Effect of Combined Mutations in DNMT3A, FLT3-ITD, and NPM1 Among Egyptian Acute Myeloid Leukemia Patients

The Value of FLT3, NPM1 and DNMT3A Gene Mutation Analysis in Acute Myeloid Leukemia Diagnosis

“…The same study noticed that deleterious effect of FLT3 ITD was most clinically important in cases with concomitant DNMT3A and NPM1 mutations (8). The frequency of triple NPM1, DNMT3A and FLT3-ITD combined mutations was lower in AML patients from Egypt (1.6%) (14) than that reported by Papaemmanuil et al (8) for AML cases included in three multicenter clinical trials of the German-Austrian AML Study Group. Presence of NPM1, DNMT3A and FLT3 ITD triple combined mutations was associated with a short survival in Egyptian AML patents (14).…”

“…FLT3 mutation testing is recommended in all AML patients in parallel with cytogenetic analyses as finding a FLT3 gene mutation is a negative prognostic marker and Midostaurin, a FLT3 TKI targeted therapy, is available (12). In addition, FLT3 gene mutation may be used as a predictor for relapse in AML, had a negative effect on survival time (13), and is frequent in older patients (14). Considering the fact that FLT3-ITD is acquired late in leukemogenesis and that FLT3-ITD mutation may be lost at the time of relapse, it is not recommended to use FLT3 mutation as a marker for minimal residual disease (MRD) monitoring (9).…”

“…NPM1 mutations are the commonest AML mutations identified up to now in adult patients, occurring in about 30% of cases, including half of cytogenetically normal AML patients and it is asso ciated with a good prognosis in the absence of FLT3 ITD mutation (14,15). NPM1 mutations were almost always found in association with co-occurrence mutations and reported usually as late driver secondary events (8).…”

“…Mutations in DNMT3A gene are associated with poor prognosis and with a higher relapse rate (4). Recently it was reported that in the absence of high-risk cytogenetics, DNMT3A mutation status has a negative impact on prognostic outcome in the presence or absence of FLT3 and/or NPM1 mutation (6,14). DNMT3A mutation is an important predictor of shorter overall survival (OS) in patients diagnosed with AML, especially in those with normal karyotype or intermediate-risk cytogenetics.…”

“…Based on their findings, presence of FLT3 ITD+ and DNMT3A R882+ double mutations represent an unfavorable prognostic factor in AML patients even after allogeneic hematopoietic stem cell transplantation (22). Recently it was reported that FLT3 ITD+ and DNMT3A R882+ double mutation is significantly associated with a lower OS (P=0.016) and it has a significant negative effect on complete remission rates (14).…”