Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1

Osamu Tomita; Kazutoshi Iijima; Takeshi Ishibashi; Tomoo Osumi; Kenichiro Kobayashi; Hajime Okita; Masahiro Saito; Tetsuya Mori; Toshiaki Shimizu; Nobutaka Kiyokawa

doi:10.1016/j.leukres.2013.11.017

Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1

Osamu Tomita, Kazutoshi Iijima, Takeshi Ishibashi, Tomoo Osumi, Kenichiro Kobayashi, Hajime Okita, Masahiro Saito, Tetsuya Mori, Toshiaki Shimizu, Nobutaka Kiyokawa

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

17 Citations (Scopus)

Abstract

We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be used for the treatment of patients with SNX2-ABL1+ ALL.

Original language	English
Pages (from-to)	361-370
Number of pages	10
Journal	Leukemia Research
Volume	38
Issue number	3
DOIs	https://doi.org/10.1016/j.leukres.2013.11.017
Publication status	Published - 2014 Mar
Externally published	Yes

Keywords

Acute lymphoblastic leukemia
BCR-ABL1
Phosphorylation
SNX2-ABL1
Tyrosine kinase inhibitor

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.2013.11.017

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title = "Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1",

abstract = "We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be used for the treatment of patients with SNX2-ABL1+ ALL.",

keywords = "Acute lymphoblastic leukemia, BCR-ABL1, Phosphorylation, SNX2-ABL1, Tyrosine kinase inhibitor",

author = "Osamu Tomita and Kazutoshi Iijima and Takeshi Ishibashi and Tomoo Osumi and Kenichiro Kobayashi and Hajime Okita and Masahiro Saito and Tetsuya Mori and Toshiaki Shimizu and Nobutaka Kiyokawa",

year = "2014",

month = mar,

doi = "10.1016/j.leukres.2013.11.017",

language = "English",

volume = "38",

pages = "361--370",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Limited",

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TY - JOUR

T1 - Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1

AU - Tomita, Osamu

AU - Iijima, Kazutoshi

AU - Ishibashi, Takeshi

AU - Osumi, Tomoo

AU - Kobayashi, Kenichiro

AU - Okita, Hajime

AU - Saito, Masahiro

AU - Mori, Tetsuya

AU - Shimizu, Toshiaki

AU - Kiyokawa, Nobutaka

PY - 2014/3

Y1 - 2014/3

N2 - We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be used for the treatment of patients with SNX2-ABL1+ ALL.

AB - We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be used for the treatment of patients with SNX2-ABL1+ ALL.

KW - Acute lymphoblastic leukemia

KW - BCR-ABL1

KW - Phosphorylation

KW - SNX2-ABL1

KW - Tyrosine kinase inhibitor

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U2 - 10.1016/j.leukres.2013.11.017

DO - 10.1016/j.leukres.2013.11.017

M3 - Article

C2 - 24367893

AN - SCOPUS:84894265023

SN - 0145-2126

VL - 38

SP - 361

EP - 370

JO - Leukemia Research

JF - Leukemia Research

IS - 3

ER -

Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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