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.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Kawai H,Matsushita H,Suzuki R,Sheng Y,Lu J,Matsuzawa H,Yahata T,Tsuma-Kaneko M,Tsukamoto H,Kawada H,Ogawa Y,Ando K

doi

10.1016/j.leukres.2014.08.015

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

1451-9

issue

12

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(14)00260-4

journal_volume

38

pub_type

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