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Updated: Apr 24, 2026
Associated Chromosome Trap for Identifying Long-range DNA Interactions
Published on: April 23, 2011
Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia
Hidetsugu Kawai1, Hiromichi Matsushita2, Rikio Suzuki3
1Research Center for Cancer Stem Cell, Tokai University School of Medicine, Isehara, Kanagawa, Japan; Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
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.
