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

• DOI: 10.1007/s00277-012-1580-5
• Publication Date: 2012-09-27T22:41:54Z
• Authors: 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
• Keywords: Adult; 0303 health sciences; Korea; Adolescent; Chromosomes, Human, Pair 21; Core Binding Factors; Cytarabine; Hematopoietic Stem Cell Transplantation; Exons; Kaplan-Meier Estimate; Combined Modality Therapy; Disease-Free Survival; 3. Good health; 03 medical and health sciences; Antineoplastic Combined Chemotherapy Protocols; Chromosome Inversion; Core Binding Factor Alpha 2 Subunit; Humans; Female; Idarubicin; Chromosomes, Human, Pair 16; Aged; Chromosomes, Human, Pair 8

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.