KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement.
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.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Hee-Jin
HJ
Kim
Hee Kyung
HK
Ahn
Chul Won
CW
Jung
Joon Ho
JH
Moon
Chang-Hun
CH
Park
Ki-O
KO
Lee
Sun-Hee
SH
Kim
Yeo-Kyeoung
YK
Kim
Hyeoung-Joon
HJ
Kim
Sang Kyun
SK
Sohn
Sung Hyun
SH
Kim
Won Sik
WS
Lee
Kyoung Ha
KH
Kim
Yeung-Chul
YC
Mun
Hawk
H
Kim
Jinny
J
Park
Woo-Sung
WS
Min
Hee-Je
HJ
Kim
Dong Hwan Dennis
DH
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000648:ultrastructure; D003131:Combined Modality Therapy; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D050660:Core Binding Factors / Q000032:analysis / Q000235:genetics; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005091:Exons / Q000235:genetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007723:Korea / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D017354:Point Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
D050676:Core Binding Factor Alpha 2 Subunit; D050660:Core Binding Factors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors; D003561:Cytarabine; C015019:enocitabine; D019009:Proto-Oncogene Proteins c-kit; D015255:Idarubicin