Functional proteomic profiling of AML predicts response and survival.
Because 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 phosphoproteins from apoptosis, cell-cycle, and signal-transduction pathways, using reverse-phase protein arrays. 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 French-American-British 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 FMS-like tyrosine kinase 3-internal tandem duplication 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 morphologic features, cytogenetics, and outcome. Confirmation in independent studies may also provide pathophysiologic insights facilitating triage of patients to emerging targeted therapies.
Departments of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Steven M
SM
Kornblau
Raoul
R
Tibes
Yi Hua
YH
Qiu
Wenjing
W
Chen
Hagop M
HM
Kantarjian
Michael
M
Andreeff
Kevin R
KR
Coombes
Gordon B
GB
Mills
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D001798:Blood Proteins / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D005260:Female; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D040901:Proteomics; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D055815:Young Adult
D000906:Antibodies; D001798:Blood Proteins