Expression and activity of Fyn mediate proliferation and blastic features of chronic myelogenous leukemia.
Expression and activity of Fyn mediate proliferation and blastic features of chronic myelogenous leukemia.
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DOI：
10.1371/journal.pone.0051611
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chandra J
中科院分区：
文献类型：
--
作者：
Singh MM;Howard A;Irwin ME;Gao Y;Lu X;Multani A;Chandra J
The BCR-ABL1 oncogene is a tyrosine kinase that activates many signaling pathways, resulting in the induction of chronic myeloid leukemia (CML). Kinase inhibitors, such as imatinib, have been developed for the treatment of CML; however, the terminal, blast crisis phase of the disease remains a clinical challenge. Blast crisis CML is difficult to treat due to resistance to tyrosine kinase inhibitors, increased genomic instability and acquired secondary mutations. Our recent studies uncovered a role for Fyn in promoting BCR-ABL1 mediated cell growth and sensitivity to imatinib. Here we demonstrate that Fyn contributes to BCR-ABL1 induced genomic instability, a feature of blast crisis CML. Bone marrow cells and mouse embryonic fibroblasts derived from Fyn knockout mice transduced with BCR-ABL1 display slowed growth and clonogenic potential as compared to Fyn wild-type BCR-ABL1 expressing counterparts. K562 cells overexpressing constitutively active Fyn kinase were larger in size and displayed an accumulation of genomic abnormalities such as chromosomal aberrations and polyploidy. Importantly, loss of Fyn protected mouse embryonic fibroblast cells from increased number of chromosomal aberrations and fragments induced by BCR-ABL1. Together, these results reveal a novel role for Fyn in regulating events required for genomic maintenance and suggest that Fyn kinase activity plays a role in the progression of CML to blast crisis.
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影响因子：
64.5
作者：
GROFFEN, J;STEPHENSON, JR;GROSVELD, G
通讯作者：
GROSVELD, G
影响因子：
11.2
作者：
Fenouille, Nina;Puissant, Alexandre;Auberger, Patrick
通讯作者：
Auberger, Patrick
影响因子：
4.8
作者：
Lam, LT;Ronchini, C;Bresnick, EH
通讯作者：
Bresnick, EH
影响因子：
37.3
作者：
Dingemans AM;van den Boogaart V;Vosse BA;van Suylen RJ;Griffioen AW;Thijssen VL
通讯作者：
Thijssen VL
影响因子：
4.8
作者：
BOLEN, JB;ROWLEY, RB;TSYGANKOV, AY
通讯作者：
TSYGANKOV, AY