Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

Yuichi Ishikawa, Naomi Kawashima, Yoshiko Atsuta, Isamu Sugiura, Masashi Sawa, Nobuaki Dobashi, Hisayuki Yokoyama, Noriko Doki, Akihiro Tomita, Toru Kiguchi, Shiro Koh, Heiwa Kanamori, Noriyoshi Iriyama, Akio Kohno, Yukiyoshi Moriuchi, Noboru Asada, Daiki Hirano, Kazuto Togitani, Toru Sakura, Maki HagiharaTatsuki Tomikawa, Yasuhisa Yokoyama, Norio Asou, Shigeki Ohtake, Itaru Matsumura, Yasushi Miyazaki, Tomoki Naoe, Hitoshi Kiyoi

Research output: Contribution to journalArticle

Abstract

The prognostic impact of KIT mutation on core-binding factor acute myeloid leukemia (CBFAML) remains controversial. We registered 199 newly diagnosed de novo CBF-AML patients, aged 16 to 64 years, who achieved complete remission. They received 3 courses of high-dose cytarabine therapy and no further treatment until hematological relapse. Mutations in exons 8, 10-11, and 17 of the KIT gene were analyzed. Furthermore, we analyzed mutations in 56 genes that are frequently identified in myeloid malignancies and evaluated minimal residual disease (MRD). The primary end point was relapse-free survival (RFS) according to KIT mutations. The RFS in KIT-mutated patients was inferior to that in unmutated patients (hazard ratio, 1.92; 95% confidence interval, 1.23-3.00; P 5 .003). Based on subgroup analysis, KIT mutations had a prognostic impact in patients with RUNX1-RUNX1T1, but not in those with CBFB-MYH11, and only exon 17 mutation had a significant prognostic impact. Multivariate Cox regression analysis with stepwise selection revealed that the KIT exon 17 mutation and the presence of extramedullary tumors in patients with RUNX1-RUNX1T1, and loss of chromosome X or Y and NRAS mutation in patients with CBFB-MYH11 were poor prognostic factors for RFS. MRD was evaluated in 112 patients, and it was associated with a poorer RFS in the patients with CBFB-MYH11, but not in those with RUNX1-RUNX1T1. These results suggested that it is necessary to separately evaluate AML with RUNX1-RUNX1T1 or CBFB-MYH11 according to appropriate prognostic factors.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalBlood Advances
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 14 2020

ASJC Scopus subject areas

  • Hematology

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    Ishikawa, Y., Kawashima, N., Atsuta, Y., Sugiura, I., Sawa, M., Dobashi, N., Yokoyama, H., Doki, N., Tomita, A., Kiguchi, T., Koh, S., Kanamori, H., Iriyama, N., Kohno, A., Moriuchi, Y., Asada, N., Hirano, D., Togitani, K., Sakura, T., ... Kiyoi, H. (2020). Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11. Blood Advances, 4(1), 66-75. https://doi.org/10.1182/bloodadvances.2019000709