Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia

Hidetsugu Kawai; Hiromichi Matsushita; Rikio Suzuki; Yin Sheng; Jun Lu; Hideyuki Matsuzawa; Takashi Yahata; Mitsuyo Tsuma-Kaneko; Hideo Tsukamoto; Hiroshi Kawada; Yoshiaki Ogawa; Kiyoshi Ando

doi:10.1016/j.leukres.2014.08.015

Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia

Hidetsugu Kawai, Hiromichi Matsushita, Rikio Suzuki, Yin Sheng, Jun Lu, Hideyuki Matsuzawa, Takashi Yahata, Mitsuyo Tsuma-Kaneko, Hideo Tsukamoto, Hiroshi Kawada, Yoshiaki Ogawa, Kiyoshi Ando

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1451-1459
Number of pages	9
Journal	Leukemia Research
Volume	38
Issue number	12
DOIs	https://doi.org/10.1016/j.leukres.2014.08.015
Publication status	Published - 2014 Dec 1
Externally published	Yes

Keywords

ABL1 fusion gene
SEPT9-ABL1
Tyrosine kinase inhibitors

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2014.08.015

Cite this

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title = "Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia",

abstract = "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.",

keywords = "ABL1 fusion gene, SEPT9-ABL1, Tyrosine kinase inhibitors",

author = "Hidetsugu Kawai and Hiromichi Matsushita and Rikio Suzuki and Yin Sheng and Jun Lu and Hideyuki Matsuzawa and Takashi Yahata and Mitsuyo Tsuma-Kaneko and Hideo Tsukamoto and Hiroshi Kawada and Yoshiaki Ogawa and Kiyoshi Ando",

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doi = "10.1016/j.leukres.2014.08.015",

language = "English",

volume = "38",

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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

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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Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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