KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement

Hee-Jin Kim; Hee Kyung Ahn; Chul Won Jung; Joon Ho Moon; Chang-Hun Park; Ki-O Lee; Sun-Hee Kim; Yeo-Kyeoung Kim; Hyeoung-Joon Kim; Sang Kyun Sohn; Sung Hyun Kim; Won Sik Lee; Kyoung Ha Kim; Yeung-Chul Mun; Hawk Kim; Jinny Park; Woo-Sung Min; Hee-Je Kim; Dong Hwan Dennis Kim; L/MDS working party, Korean Society of Hematology

doi:10.1007/s00277-012-1580-5

KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement

Ann Hematol. 2013 Jan;92(2):163-71. doi: 10.1007/s00277-012-1580-5. Epub 2012 Sep 28.

Affiliation

¹ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

PMID: 23053179
DOI: 10.1007/s00277-012-1580-5

Abstract

Core binding factor (CBF)-positive acute myeloid leukemia (AML) presents a favorable prognosis, except for patients with KIT mutation, especially D816 mutation. The current retrospective study attempted to validate a prognostic role of KIT mutation in 121 Korean patients with CBF AML. The study patients consisted of 121 patients with CBF AML (82 patients with RUNX1/RUNX1T1 [67.8 %] and 39 patients with CBFB/MYH11 [32.2 %]) recruited from eight institutions in Korea. All patients received idarubicin plus cytarabine or behenoyl cytosine arabinoside 3 + 7 induction chemotherapy. The KIT gene mutation status was determined by direct sequencing analyses. A KIT mutation was detected in 32 cases (26.4 %) in our series of patients. The KIT mutation was most frequent in exon 17 (n = 18, 14.9 %; n = 16 with D816 mutation), followed by exon 8 (n = 10, 8.3 %). The presence of KIT D816 mutation was associated with adverse outcomes for the event-free survival (p = 0.03) and for the overall survival (p = 0.02). The unfavorable impact of D816 mutation was more prominent when the analysis was confined to the RUNX1/RUNX1T1 subtype. The KIT mutation was detected in 26.4 % of Korean patients with CBF AML. The KIT D816 mutation demonstrated an unfavorable prognostic implication, particularly in the RUNX1/RUNX1T1 subtype.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Chromosome Inversion
Chromosomes, Human, Pair 16 / genetics
Chromosomes, Human, Pair 16 / ultrastructure
Chromosomes, Human, Pair 21 / genetics
Chromosomes, Human, Pair 21 / ultrastructure
Chromosomes, Human, Pair 8 / genetics
Chromosomes, Human, Pair 8 / ultrastructure
Combined Modality Therapy
Core Binding Factor Alpha 2 Subunit / genetics*
Core Binding Factors / analysis
Core Binding Factors / genetics
Cytarabine / administration & dosage
Cytarabine / analogs & derivatives
Disease-Free Survival
Exons / genetics
Female
Hematopoietic Stem Cell Transplantation
Humans
Idarubicin / administration & dosage
Kaplan-Meier Estimate
Korea / epidemiology
Leukemia, Myeloid, Acute / drug therapy
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / surgery
Male
Middle Aged
Neoplasm Proteins / analysis
Neoplasm Proteins / genetics*
Point Mutation*
Prognosis
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-kit / genetics*
RUNX1 Translocation Partner 1 Protein
Transcription Factors / genetics*
Translocation, Genetic
Treatment Outcome
Young Adult

Substances

Core Binding Factor Alpha 2 Subunit
Core Binding Factors
Neoplasm Proteins
Proto-Oncogene Proteins
RUNX1 Translocation Partner 1 Protein
RUNX1 protein, human
RUNX1T1 protein, human
Transcription Factors
Cytarabine
enocitabine
Proto-Oncogene Proteins c-kit
Idarubicin