title: Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A.
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.
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Jo
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.|Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. korailman-1@hanmail.net.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: In Suk
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.|Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Jongyoun
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.|Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Hyung Hoi
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Chulhun L
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.|Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. eylee@pusan.ac.kr.
authors.forename: Eun Yup
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Young Uk
authors.initials: YU
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Chan Jeoung
authors.initials: CJ
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Chi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D003561:Cytarabine; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D003630:Daunorubicin
keywords: AML; Monitoring; NPM1 type A mutation; Quantitation; Real-time PCR