Functional proteomic profiling of AML predicts response and survival

Steven M. Kornblau, Raoul Tibes, Yi Hua Qiu, Wenjing Chen, Hagop M. Kantarjian, Michael Andreeff, Kevin R. Coombes, Gordon Mills

Research output: Contribution to journalReview article

161 Citations (Scopus)

Abstract

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 proteomicbased classification of acute myeloid leukemia (AML), we assayed leukemiaenriched 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 leukemiaenriched 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.

Original languageEnglish (US)
Pages (from-to)154-164
Number of pages11
JournalBlood
Volume113
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Acute Myeloid Leukemia
Proteomics
Survival
Proteins
Cytogenetics
Bone Marrow
Protein Array Analysis
Triage
Phosphoproteins
Signal transduction
Principal Component Analysis
Chromosome Aberrations
Protein-Tyrosine Kinases
Signal Transduction
Cell Cycle
Principal component analysis
Apoptosis
Blood
Recurrence
Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kornblau, S. M., Tibes, R., Qiu, Y. H., Chen, W., Kantarjian, H. M., Andreeff, M., ... Mills, G. (2009). Functional proteomic profiling of AML predicts response and survival. Blood, 113(1), 154-164. https://doi.org/10.1182/blood-2007-10-119438

Functional proteomic profiling of AML predicts response and survival. / Kornblau, Steven M.; Tibes, Raoul; Qiu, Yi Hua; Chen, Wenjing; Kantarjian, Hagop M.; Andreeff, Michael; Coombes, Kevin R.; Mills, Gordon.

In: Blood, Vol. 113, No. 1, 01.01.2009, p. 154-164.

Research output: Contribution to journalReview article

Kornblau, SM, Tibes, R, Qiu, YH, Chen, W, Kantarjian, HM, Andreeff, M, Coombes, KR & Mills, G 2009, 'Functional proteomic profiling of AML predicts response and survival', Blood, vol. 113, no. 1, pp. 154-164. https://doi.org/10.1182/blood-2007-10-119438
Kornblau SM, Tibes R, Qiu YH, Chen W, Kantarjian HM, Andreeff M et al. Functional proteomic profiling of AML predicts response and survival. Blood. 2009 Jan 1;113(1):154-164. https://doi.org/10.1182/blood-2007-10-119438
Kornblau, Steven M. ; Tibes, Raoul ; Qiu, Yi Hua ; Chen, Wenjing ; Kantarjian, Hagop M. ; Andreeff, Michael ; Coombes, Kevin R. ; Mills, Gordon. / Functional proteomic profiling of AML predicts response and survival. In: Blood. 2009 ; Vol. 113, No. 1. pp. 154-164.
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