title: Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia.
abstract: KIT exon 17 mutation is a poor prognostic factor in core-binding factor acute myeloid leukemia. However, the mutation detection method used for risk assessment is not assigned. It is necessary to verify the analytical and clinical performance before applying new methods. Herein, we firstly applied a highly sensitive allele-specific, real-time quantitative PCR (AS-qPCR) assay to analyze KIT mutations, which demonstrated excellent sensitivity and specificity. Much higher incidence of KIT mutations (62.2%, 69/111) and prevalence of multiple mutations (43.5%, 30/69) were observed using AS-qPCR, which meant the existence of multiple KIT mutant subclones. The relative KIT mutant level was variable (median, 0.3 per control allele 100 copies, 0.002-532.7) and was divided into two groups: high (⩾10, n=26) and low (<10) mutant level. Interestingly, rather than mutation positivity, mutant level was found to be associated with clinical outcome. High mutant level showed significantly inferior overall survival (P=0.005) and event-free survival (P=0.03), whereas low level did not influence the prognosis. The follow-up data showed that the mutant level were along with fusion transcripts in the majority (n=29), but moved separately in some cases, including the loss of mutations (n=5) and selective proliferation of minor clones (n=2) at relapse. This study highlighted that the KIT mutation should be analyzed using sensitive and quantitative techniques and set a cutoff level for identifying the risk group.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: W
authors.initials: W
authors.lastname: Jang
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.affiliation: Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: G D
authors.initials: GD
authors.lastname: Lee
authors.affiliation: Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: A
authors.initials: A
authors.lastname: Kwon
authors.affiliation: Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Inha University, Incheon, Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Nahm
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: W-S
authors.initials: WS
authors.lastname: Min
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Catholic Genetic Laboratory Center, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D050660:Core Binding Factors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D050660:Core Binding Factors; D019009:Proto-Oncogene Proteins c-kit