Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A

Abstract

BackgroundNucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose.MethodsTwenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared.ResultsThe median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis.ConclusionsThe NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation.

Flow Cytometry and Molecular Techniques Could Complement Morphological Detection of Leukemic Infiltration in Ascitic Fluids: A Case Report

“…The prognostic implications of this specific immunophenotypic profile are not well known, although some studies show a greater overall survival in these patients [8]. We have no explanation for the discordant results between morphological blast count and NPM1 quantitation in BM performed after the second cycle of chemotherapy, given that these measurements seem to be very concordant [9].…”

Progression inference for somatic mutations in cancer

“…There were five main root nodes observed for mutations in FLT3, IDH2, NPM1, TP53, and upregulation of RAD21. Most of these mutations have been observed previously in AML [191] , [192] , [201] , [192] , [210] , [211] . Our first tree shows that mutations in FLT3 will precede mutations in WT1 [193] .…”

Molecular study of Nucleophosmin 1(NPM1) gene in acute myeloid leukemia in Kurdish population

“…6 A good molecular marker for assessing the clinical status and predicting the outcomes in AML patients was Nucleophosmin 1 gene (NPM1) mutation. 14 Webersinke et al reported that as primary leukemogenic the mutations in exon 12 of the nucleophosmin (NPM1) gene have been described and event in up to 35% of adult acute myelogenous leukemia (AML) cases and they added that this type of AML is listed as provisional entity in the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues. 15 Juliusson and Colleagues reported that mutations in Nucleophosmin 1 (NPM1) provide prognostic information with clinical relevance through choice of treatment and they found that significantly females more often had NPM1 mutation than male.…”

“… 6 A good molecular marker for assessing the clinical status and predicting the outcomes in AML patients was Nucleophosmin 1 gene (NPM1) mutation. 14 …”