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Proc Natl Acad Sci U S A. 2006 Feb 13; [Epub ahead of print]
Gene _expression_ changes associated with progression and response in chronic myeloid leukemia.
Radich JP, Dai H, Mao M, Oehler V, Schelter J, Druker B, Sawyers C, Shah N, Stock W, Willman CL, Friend S, Linsley PS.
Divisions of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; Rosetta Inpharmatics, Seattle, WA 98109; Oregon Health & Science University, University Center, Portland, OR 97239; University of California, Los Angeles, CA 90095; University of Chicago School of Medicine, Chicago, IL 60637; University of New Mexico Cancer Research and Treatment Center, Albuquerque, NM 87131.
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease with distinct biological and clinical features. The biologic basis of the stereotypical progression from chronic phase through accelerated phase to blast crisis is poorly understood. We used DNA microarrays to compare gene _expression_ in 91 cases of CML in chronic (42 cases), accelerated (17 cases), and blast phases (32 cases). Three thousand genes were found to be significantly (P < 10(-10)) associated with phase of disease. A comparison of the gene signatures of chronic, accelerated, and blast phases suggest that the progression of chronic phase CML to advanced phase (accelerated and blast crisis) CML is a two-step rather than a three-step process, with new gene _expression_ changes occurring early in accelerated phase before the accumulation of increased numbers of leukemia blast cells. Especially noteworthy and potentially significant in the progression program were the deregulation of the WNT/beta-catenin pathway, the decreased _expression_ of Jun B and Fos, alternative kinase deregulation, such as Arg (Abl2), and an increased _expression_ of PRAME. Studies of CML patients who relapsed after initially successful treatment with imatinib demonstrated a gene _expression_ pattern closely related to advanced phase disease. These studies point to specific gene pathways that might be exploited for both prognostic indicators as well as new targets for therapy.
PMID: 16477019 [PubMed - as supplied by publisher]
The full text article is available free at www.pnas.org
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