Journal Article

Clinical significance of ASXL2 and ZBTB7A mutations and C-terminally truncated RUNX1-RUNX1T1 expression in AML patients with t(8;21) enrolled in the JALSG AML201 study

Ishikawa, Yuichi, Sakaida, Emiko, Sakura, Toru, Suehiro, Youko, Usui, Noriko, Ogawa, Seishi, Miyazaki, Yasushi, Kiyoi, Hitoshi, Akashi, Akimi, Suzushima, Hitoshi, Kanamori, Heiwa, Ohtake, Shigeki, Takeshita, Akihiro, Kawashima, Naomi, Ozawa, Yukiyasu, Kihara, Rika, Naoe, Tomoki, Asou, Norio, Miyawaki, Shuichi, Ito, Yoshikazu, Kitamura, Kunio, Nagata, Yasunobu, Imai, Kiyotoshi, Matsumura, Itaru

2019

Overview

We analyzed the clinical significance and genetic features of ASXL2 and ZBTB7A mutations, and the alternatively spliced isoform of the RUNX1-RUNX1T1 transcript, which is also called AML1-ETO9a (AE9a), in Japanese CBF-AML patients enrolled in the JALSG AML201 study. ASXL2 and ZBTB7A genes were sequenced using bone marrow samples of 41 AML patients with t(8;21) and 14 with inv(16). The relative expression levels of AE9a were quantified using the real-time PCR assay in 23 AML patients with t(8;21). We identified ASXL2 (34.1%) and ZBTB7A (9.8%) mutations in only AML patients with t(8;21). ASXL2-mutated patients had a significantly higher WBC count at diagnosis (P = 0.04) and a lower frequency of sex chromosome loss than wild-type patients (33 vs. 76%, respectively, P = 0.01). KIT mutations were the most frequently accompanied with both ASXL2 (36%) and ZBTB7A (75%) mutations. Neither ASXL2 nor ZBTB7A mutations had an impact on overall or event-free survival. Patients harboring cohesin complex gene mutations expressed significantly higher levels of AE9a than unmutated patients (P = 0.03). In conclusion, ASXL2 and ZBTB7A mutations were frequently identified in Japanese AML patients with t(8;21), but not in those with inv(16). Further analysis is required to clarify the detailed biological mechanism of AE9a regulation of the cohesin complex.

• Publisher: Springer Nature B.V
• Subject: Clinical significance / Mutation