TY - JOUR
T1 - Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia
AU - Kawai, Hidetsugu
AU - Matsushita, Hiromichi
AU - Suzuki, Rikio
AU - Sheng, Yin
AU - Lu, Jun
AU - Matsuzawa, Hideyuki
AU - Yahata, Takashi
AU - Tsuma-Kaneko, Mitsuyo
AU - Tsukamoto, Hideo
AU - Kawada, Hiroshi
AU - Ogawa, Yoshiaki
AU - Ando, Kiyoshi
N1 - Funding Information:
We thank Dr. Warren S. Pear (University of Pennsylvania) for providing the MIGR1 retroviral vector, Dr. Toshio Kitamura (The University of Tokyo) for providing the PLAT-gp packaging cells, and Ms. Akemi Kamijo, Ms. Katsuko Naito, Ms. Yoshiko Ito and Mr. Masayuki Tanaka (Biological Science Support Center, Tokai University) for their professional technical assistance. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Nos. 24390248 and 24591411 ), Tokai University School of Medicine Project Research in Japan.
Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - We analyzed the function of a SEPT9-ABL1 fusion identified in a case of T-prolymphocytic leukemia with tyrosine kinase inhibitor (TKI) resistance. Five isoforms with different N-termini, including SEPT9a-ABL1, SEPT9b-ABL1, SEPT9d-ABL1, SEPT9e-ABL1 and SEPT9f-ABL1, were detected in the leukemic cells. All isoforms except SEPT9d-ABL1 are localized in the cytoplasm, undergo autophosphorylation and phosphorylate the downstream targets, STAT-5 and Crkl, and provided IL-3-independence and in vivo invasiveness to 32D cells. Additionally, these SEPT9-ABL1 isoforms were resistant to TKIs in vitro and in vivo, in comparison to BCR-ABL1. These findings demonstrated that SEPT9-ABL1 had oncogenic activity and conferred resistance to TKIs.
AB - We analyzed the function of a SEPT9-ABL1 fusion identified in a case of T-prolymphocytic leukemia with tyrosine kinase inhibitor (TKI) resistance. Five isoforms with different N-termini, including SEPT9a-ABL1, SEPT9b-ABL1, SEPT9d-ABL1, SEPT9e-ABL1 and SEPT9f-ABL1, were detected in the leukemic cells. All isoforms except SEPT9d-ABL1 are localized in the cytoplasm, undergo autophosphorylation and phosphorylate the downstream targets, STAT-5 and Crkl, and provided IL-3-independence and in vivo invasiveness to 32D cells. Additionally, these SEPT9-ABL1 isoforms were resistant to TKIs in vitro and in vivo, in comparison to BCR-ABL1. These findings demonstrated that SEPT9-ABL1 had oncogenic activity and conferred resistance to TKIs.
KW - ABL1 fusion gene
KW - SEPT9-ABL1
KW - Tyrosine kinase inhibitors
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U2 - 10.1016/j.leukres.2014.08.015
DO - 10.1016/j.leukres.2014.08.015
M3 - Article
C2 - 25217890
AN - SCOPUS:84916218774
SN - 0145-2126
VL - 38
SP - 1451
EP - 1459
JO - Leukemia Research
JF - Leukemia Research
IS - 12
ER -
