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

• Published in: Annals of laboratory medicine Vol. 36; no. 5; pp. 399 - 404
• Main Authors: Jo, Su Yeon, Park, Sang Hyuk, Kim, In-Suk, Yi, Jongyoun, Kim, Hyung-Hoi, Chang, Chulhun L., Lee, Eun Yup, Cho, Young-Uk, Jang, Seongsoo, Park, Chan-Jeoung, Chi, Hyun-Sook
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society for Laboratory Medicine 01.09.2016; 대한진단검사의학회
• Subjects: Antineoplastic Agents - therapeutic use; Bone Marrow - metabolism; Bone Marrow - pathology; Cytarabine - therapeutic use; Daunorubicin; fms-Like Tyrosine Kinase 3 - genetics; Humans; Karyotype; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Original; Real-Time Polymerase Chain Reaction; Recurrence; Remission Induction; Retrospective Studies; Sequence Analysis, DNA; 병리학; AML; Quantitation; Real-time PCR; Monitoring; NPM1 type A mutation
• ISSN: 2234-3806; 2234-3814; 2234-3814
• DOI: 10.3343/alm.2016.36.5.399

Nucleophosmin 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. Twenty-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. The 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. The 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.