Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cell Mol Med. 2007 Nov-Dec;11(6):1251-62. doi: 10.1111/j.1582-4934.2007.00108.x.

Stem cell and kinase activity-independent pathway in resistance of leukaemia to BCR-ABL kinase inhibitors.

Author information

1
The Jackson Laboratory, Bar Harbor, ME, USA. shaoguang.li@jax.org

Abstract

BCR-ABL tyrosine kinase inhibitors, such as imatinib (Gleevec) are highly effective in treating human Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in chronic phase but not in terminal acute phase; acquired drug resistance caused mainly by the development of BCR-ABL kinase domain mutations prevents cure of the leukaemia. In addition, imatinib is ineffective in treating Ph+ B-cell acute lymphoblastic leukaemia (B-ALL) and CML blast crisis, even in the absence of the kinase domain mutations. This type of drug resistance that is unrelated to BCR-ABL kinase domain mutations is caused by the insensitivity of leukaemic stem cells to kinase inhibitors such as imatinib and dasatinib, and by activation of a newly-identified signalling pathway involving SRC kinases that are independent of BCR-ABL kinase activity for activation. This SRC pathway is essential for leukaemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis. Apart from BCR-ABL and SRC kinases, stem cell pathways must also be targeted for curative therapy of Ph+ leukaemia.

PMID:
18205699
PMCID:
PMC4401291
DOI:
10.1111/j.1582-4934.2007.00108.x
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center