Association between increased mutation rates in DNMT3Α and FLT3‑ITD and poor prognosis of patients with acute myeloid leukemia

Abstract

A total of 133 patients with acute myeloid leukemia (AML) were enrolled in the current study and were subdivided into 4 groups: 34 harboring DNA methyltransferase 3 α (DNMT3A) + fms related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, 37 harboring only FLT3-ITD mutation, 32 harboring only DNMT3A mutation and 30 harboring no mutations in DNMT3A and FLT3-ITD (control). Patients in all groups were administered daunorubicin and cytarabine chemotherapy regimens. The rates of complete remission (CR), 1-year relapse (RR) and 3-year overall survival (OS) were compared. Patients in the DNMT3A + FLT3-ITD mutation group exhibited higher proportions of peripheral white blood cells (WBCs) and myeloid progenitor cells compared with those in DNMT3A mutation only, FLT3-ITD mutation only and control groups (P<0.05). The rates of CD15 + and HLA-DR + in the DNMT3A + FLT3-ITD mutation and DNMT3A mutation only groups were significantly higher than those in the FLT3-ITD mutation only and control groups (P<0.05); in addition, the rate of CD38 + in the DNMT3A + FLT3-ITD mutation and FLT3-ITD mutation only groups was significantly higher compared with that in the DNMT3A mutation only and control groups (P<0.05). The overall chemotherapy effectiveness rate, CR, 1-year RR and the 3-year OS rates of patients in the DNMT3A + FLT3-ITD mutation group were significantly worse compared with FLT3-ITD mutation only, DNMT3A mutation only and control groups (P<0.05). The results of this study indicated that increased mutation rates in DNMT3Α and FLT3-ITD may be associated with increased WBC and myeloid progenitor cell counts, an inferior chemotherapy efficacy and prognosis, a lower CR rate, and higher 1-year RR and mortality rate.

FLT3-ITD Mutation and FLT3 Ligand Plasma Level Were Not Associated with One-Year Survival of Indonesian Acute Myeloid Leukemia Patients

“…These findings are in concordance with two studies in Iran and Middle East but different from other studies from other countries including Japan, China, and Europe. 21,[27][28][29][30][31] For platelet level, the cohort in this study had higher median level than the study by Ni et al but similar with the study by Scholl et al 23,26 Based on higher hemoglobin level and lower leukocyte level, the cohort in his study may have better prognosis when compared with other AML studies. Level of FLT3 ligand plasma below 4.1 pg/mL were more common in FLT3-ITD mutant group in our study.…”

Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1

“…28,29 The prognostic significance of mutations in DNMT3A has been controversial, while some studies found no significant influence in survival outcome 17 others suggest that the co-occurrence of NPM1 mut /DNMT3A mut /FLT3-ITD in AML patients is associated with an adverse outcome. 7,13,[30][31][32][33] In 2013 the German AML Study Group described the clinical impact of DNMT3A in younger adults with AML. 34 In a univariable exploratory subset analysis, they showed a significant prognostic impact of DNMT3A mut in ELN-unfavorable AMLs, whereas no impact appeared in ELN-favorable AMLs.…”

CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations

“…Moreover, studies have reported that FLT3 mutations often co-occur with DNMT3A mutations, leading to a worse prognosis. 6 Internal tandem duplication (ITD) mutations of FLT3 are among the most frequent genetic alterations in AML. 7 FLT3 inhibitors improve remission rates of AML patients, but drug toxicity and acquired resistance remain significant challenges.…”