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Blood, 1 January 2009, Vol. 113, No. 1, pp. 154-164. Prepublished online as a Blood First Edition Paper on October 7, 2008; DOI 10.1182/blood-2007-10-119438.
Submitted October 29, 2007
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: skornblau{at}mdanderson.org.
Since protein function regulates the phenotypic characteristics of cancer, a functional proteomic classification system could provide important information for pathogenesis and prognosis. With the goal of ultimately developing a proteomic based classification of acute myeloid leukemia (AML), we assayed leukemia-enriched cells from 256 newly diagnosed AML patients, for 51 total and phospho-proteins from apoptosis, cell cycle, and signal transduction pathways, using reverse phase protein arrays (RPPA). Expression in matched blood and marrow samples were similar for 44 proteins; another 7 had small fold changes (8-55%), suggesting that functional proteomics of leukemia-enriched cells in the marrow and periphery are similar. Protein expression patterns were independent of clinical characteristics. However, 24 proteins were significantly different between FAB subtypes, defining distinct signatures for each. Expression signatures for AML with cytogenetic abnormalities involving - 5 or -7, were similar suggesting mechanistic commonalities. Distinct expression patterns for FLT3-ITD were also identified. Principal component analysis defined 7 protein signature groups, with prognostic information distinct from cytogenetics that correlated with remission attainment, relapse, and overall survival. In conclusion, protein expression profiling patterns in AML correlate with known morphological features, cytogenetics and outcome. Confirmation in independent studies may also provide pathophysiological insights facilitating triage of patients to emerging targeted therapies.
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