FLT3-ITD with DNMT3A R882 double mutation is a poor prognostic factor in Chinese patients with acute myeloid leukemia after chemotherapy or allogeneic hematopoietic stem cell transplantation

Abstract

To investigate clinical characteristics and outcomes of transplantation in AML patients with FLT3-ITD/DNMT3A double mutation, we retrospectively analyzed 206 Chinese patients with AML after Sanger sequencing. Our analysis showed that AML patients with FLT3-ITD and DNMT3A R882 mutations had a higher white blood cell count and a lower complete remission (CR) rate after first induction chemotherapy. All 206 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in status of CR. These results indicate that AML patients with FLT3-ITD and DNMT3A R882 double mutation show a higher 2-year cumulative incidence of relapse (CIR), lower 2-year overall survival (OS) rate, and lower 2-year leukocyte-free survival (LFS) after allo-HSCT. The univariate and multivariate analyses confirmed that disease status prior to transplantation, FLT3-ITD, FLT3-ITD, and DNMT3A R882 double mutation were independent factors for poor prognosis after allo-HSCT. In summary, the present cohort study demonstrated that FLT3-ITD and DNMT3A R882 double mutation predicts poor prognosis in Chinese AML patients receiving chemotherapy or allo-HSCT treatment.

Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification

“…Similarly, it was reported that the presence of concomitant FLT3 ITD and DNMT3A R882 mutations in patients with AML is an unfavorable prognostic factor. [28][29][30] In this study, we identified a significant association of CNAs with the FLT3 D835 mutation, but not with age, WBC and platelet counts, LDH and hemoglobin levels, blast percentage, or the ECOG performance status.…”

High expression of microRNA‑500 is associated with poor prognosis in patients with acute myeloid leukemia receiving allogeneic hematopoietic stem cell transplantation

“…This was also observed for patients with a low expression level of miR-500 in the present study. The lower expression of miR-500 was associated with a higher proportion of patients with inv (16), which may be associated with an improved prognosis. As presented in Table I, all the patients with a favorable molecular risk were in the miR-500 low group in the current study, suggesting that miR-500 expression adversely affects the prognosis of patients with AML receiving allo-HSCT.…”

“…A previous study suggested that determining the mutation status of NPM1 following allo-HSCT may predict the likelihood of relapse (14). While it was previously reported that FLT3 mutation status does not adversely impact OS time following allo-HSCT (15), another study revealed that FLT3 and DNMT3A R882 mutations were associated with poor prognosis in patients with AML receiving allo-HSCT treatment (16). The results of the current study suggested that miR-500 had an adverse effect on OS time, while mutations in the genes FLT3, NPM1 and DNMT3A were not independently associated with OS time in patents with AML receiving allo-HSCT.…”

“…A number of biomarkers are currently used for the diagnosis, prognosis evaluation and treatment strategy of patients with AML, including karyotype, molecular classifications and mutation analysis (2). Classically, specific recurrent chromosomal translocations, including inversion (16) [inv (16)], translocation (8;21) [t(8;21)] and t (15;17) indicate a positive prognosis, while chromosomal deletions (dels) including del(5q), -5 and -7 are associated with more severe disease phenotypes. Gene mutations in fms-related tyrosine kinase 3 (FLT3), DNA methyltransferase 3α (DNMT3A), KIT proto-oncogene, receptor tyrosine kinase (KIT), runt-related transcription factor 1 (RUNX1), isocitrate dehydrogenase (NADP(+))1 cytosolic and isocitrate dehydrogenase (NADP(+))2 mitochondrial indicate a poor outcome, while mutations in nucleophosmin 1 (NPM1) and CCAAT enhancer binding protein a are associated with a favorable prognosis (3,4).…”

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

“…Recently, it was reported by Tang et al that AML patients with FLT3 ITD and DNMT3A R882 double mutation had a poor prognosis, and that FLT3 ITD+ and DNMT3A R882+ double muta-tion was an independent factor for poor outcome post-transplantation (7). Another recent study performed by Ardestani et al revealed that patients with both DNMT3A R882 and FLT3 ITD mutations had the worst OS and relapse-free survival compared with AML cases with one mutation (22).…”