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PMID: 17353369 Published · ppublish English Comment Journal Article Review

Oncogenic signaling: new insights and controversies from chronic myeloid leukemia.

The Journal of experimental medicine ·Vol. 204 ·No. 3 ·2007-03-19 ·Pages 461-5

Van Etten RA

Abstract

Chronic myeloid leukemia (CML), which is caused by the BCR-ABL fusion tyrosine kinase, is one of the most intensively studied human cancers. ABL kinase inhibitors have been spectacularly successful in treating CML, but disease persistence and acquired drug resistance can prevent eradication and cure of the leukemia. The development of better therapies will depend on a full understanding of signaling pathways in CML, facilitated by model studies using mutant mice.

MeSH Terms
Animals Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology,etiology,genetics,therapy Signal Transduction/genetics,physiology
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Van Etten Richard A
Molecular Oncology Research Institute and the Division of Hematology/Oncology, Tufts-New England Medical Center, Boston, MA 02111, USA. rvanetten@tufts-nemc.org
References (34)
34 references, click to expand
  1. Overriding imatinib resistance with a novel ABL kinase inhibitor.
    Science. 2004 Jul 16;305(5682):399-401 PMID: 15256671
  2. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice.
    Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16870-5 PMID: 17077147
  3. Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation.
    Mol Cell Biol. 2004 Sep;24(18):8037-47 PMID: 15340066
  4. Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML.
    Blood. 2004 Oct 15;104(8):2532-9 PMID: 15256422
  5. Responsiveness of human granulocytic leukemic cells to colony-stimulating factor.
    Blood. 1974 Jun;43(6):847-59 PMID: 4208780
  6. Leukotriene production by fresh human bone marrow cells: evidence of altered lipoxygenase activity in chronic myelocytic leukemia.
    Exp Hematol. 1987 Feb;15(2):203-7 PMID: 3028851
  7. Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors.
    Blood. 1991 Mar 1;77(5):925-9 PMID: 1704804
  8. Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene.
    Cell. 1996 Oct 18;87(2):307-17 PMID: 8861914
  9. P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members.
    J Biol Chem. 1996 Dec 6;271(49):31704-10 PMID: 8940193
  10. Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias.
    Blood. 1998 Jan 1;91(1):22-9 PMID: 9414265
  11. Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required for leukemogenesis.
    J Exp Med. 1999 Apr 19;189(8):1229-42 PMID: 10209040
  12. Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein.
    J Exp Med. 1999 Aug 2;190(3):411-21 PMID: 10430629
  13. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML.
    N Engl J Med. 2004 Aug 12;351(7):657-67 PMID: 15306667
  14. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.
    N Engl J Med. 2006 Jun 15;354(24):2531-41 PMID: 16775234
  15. Janus kinase 2: a critical target in chronic myelogenous leukemia.
    Cancer Res. 2006 Jul 1;66(13):6468-72 PMID: 16818614
  16. Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease.
    J Exp Med. 2006 Oct 30;203(11):2529-40 PMID: 17043146
  17. Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein.
    Blood. 1999 Dec 1;94(11):3764-71 PMID: 10572090
  18. Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder.
    Mol Cell Biol. 2000 Feb;20(4):1149-61 PMID: 10648600
  19. Bcr/Abl activates transcription of the Bcl-X gene through STAT5.
    Blood. 2000 Sep 15;96(6):2269-76 PMID: 10979976
  20. Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5.
    Blood. 2000 Sep 15;96(6):2277-83 PMID: 10979977
  21. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.
    Science. 2001 Aug 3;293(5531):876-80 PMID: 11423618
  22. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro.
    Blood. 2002 Jan 1;99(1):319-25 PMID: 11756187
  23. Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5.
    Blood. 2002 Jan 15;99(2):479-87 PMID: 11781228
  24. Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice.
    Blood. 2002 Jul 1;100(1):238-45 PMID: 12070033
  25. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant Bcr-Abl kinases.
    Blood. 2003 Jan 15;101(2):664-72 PMID: 12393636
  26. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia.
    N Engl J Med. 2003 Oct 9;349(15):1423-32 PMID: 14534335
  27. Interferon consensus sequence binding protein (ICSBP; IRF-8) antagonizes BCR/ABL and down-regulates bcl-2.
    Blood. 2004 May 1;103(9):3480-9 PMID: 14656881
  28. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia.
    Nat Genet. 2004 May;36(5):453-61 PMID: 15098032
  29. Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells.
    Nat Med. 2004 Nov;10(11):1187-9 PMID: 15502840
  30. Focus on myeloproliferative diseases and myelodysplastic syndromes.
    Cancer Cell. 2004 Dec;6(6):547-52 PMID: 15607959
  31. Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning.
    J Exp Med. 2006 Jan 23;203(1):73-85 PMID: 16380511
  32. Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML).
    Blood. 2006 Apr 15;107(8):3279-87 PMID: 16278304
  33. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation.
    Blood. 2006 Jun 15;107(12):4898-906 PMID: 16493008
  34. STAT5 signaling is required for the efficient induction and maintenance of CML in mice.
    Blood. 2006 Jun 15;107(12):4917-25 PMID: 16522816
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20062335
Email
rvanetten@tufts-nemc.org
Published
2007-03-19
Epub
2007-00-12
Pages
461-5
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2137897
Subset
IM
Corrections
CommentOn
PMID: 17043146
External Links
PubMed source DOI: 10.1084/jem.20062335 PMC Full Text View journal details
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