Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A.
10.3343/alm.2016.36.5.399
- Author:
Su Yeon JO
1
;
Sang Hyuk PARK
;
In Suk KIM
;
Jongyoun YI
;
Hyung Hoi KIM
;
Chulhun L CHANG
;
Eun Yup LEE
;
Young Uk CHO
;
Seongsoo JANG
;
Chan Jeoung PARK
;
Hyun Sook CHI
Author Information
1. Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
- Publication Type:Original Article
- Keywords:
AML;
NPM1 type A mutation;
Quantitation;
Real-time PCR;
Monitoring
- MeSH:
Antineoplastic Agents/therapeutic use;
Bone Marrow/metabolism/pathology;
Cytarabine/therapeutic use;
Daunorubicin;
Humans;
Karyotype;
Leukemia, Myeloid, Acute/drug therapy/genetics/*pathology;
Mutation;
Nuclear Proteins/*genetics/metabolism;
Real-Time Polymerase Chain Reaction;
Recurrence;
Remission Induction;
Retrospective Studies;
Sequence Analysis, DNA;
fms-Like Tyrosine Kinase 3/genetics
- From:Annals of Laboratory Medicine
2016;36(5):399-404
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
