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24.09.2018 | Original 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

verfasst von: Naomi Kawashima, Akimi Akashi, Yasunobu Nagata, Rika Kihara, Yuichi Ishikawa, Norio Asou, Shigeki Ohtake, Shuichi Miyawaki, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Yoshikazu Ito, Kiyotoshi Imai, Youko Suehiro, Kunio Kitamura, Emiko Sakaida, Akihiro Takeshita, Hitoshi Suzushima, Tomoki Naoe, Itaru Matsumura, Yasushi Miyazaki, Seishi Ogawa, Hitoshi Kiyoi, for the Japan Adult Leukemia Study Group (JALSG)

Erschienen in: Annals of Hematology | Ausgabe 1/2019

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Abstract

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.

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Titel: 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
verfasst von: Naomi Kawashima
Akimi Akashi
Yasunobu Nagata
Rika Kihara
Yuichi Ishikawa
Norio Asou
Shigeki Ohtake
Shuichi Miyawaki
Toru Sakura
Yukiyasu Ozawa
Noriko Usui
Heiwa Kanamori
Yoshikazu Ito
Kiyotoshi Imai
Youko Suehiro
Kunio Kitamura
Emiko Sakaida
Akihiro Takeshita
Hitoshi Suzushima
Tomoki Naoe
Itaru Matsumura
Yasushi Miyazaki
Seishi Ogawa
Hitoshi Kiyoi
for the Japan Adult Leukemia Study Group (JALSG)
Publikationsdatum: 24.09.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 1/2019
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-018-3492-5

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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

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