Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34-positive compartment

Alfonso Quintás-Cardama, Yi Hua Qiu, Sean M. Post, Yiqun Zhang, Chad J. Creighton, Jorge Cortes, Steven M. Kornblau

Research output: Contribution to journalArticle

Abstract

Background: Chronic myeloid leukemia (CML) is a clonal stem cell malignancy whose pathogenesis is driven by constitutive activation of the breakpoint cluster region-v-abl Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) kinase. Although BCR-ABL1 activation is present in all patients with CML, patients can present in 3 different phases characterized by an increasingly worse prognosis and diminished responsiveness to tyrosine kinase inhibitors: chronic phase, accelerated phase, or blastic phase. The biologic basis for progression from chronic phase to blastic phase and for regulating the homeostasis of tyrosine kinase inhibitor-resistant CML stem cells is not entirely understood. Methods: To shed some light into these aspects of CML biology, the authors used reverse phase protein arrays probed with 112 individual monoclonal antibodies to compare protein expression patterns in 40 samples of leukemia-enriched fractions from patients with CML (25 in chronic phase, 5 in accelerated phase, and 10 in phase). Results: An analysis of variance (significance cutoff, P <.01) unveiled a set of proteins that were overexpressed in blastic phase, including heat-shock protein 90 (hsp90); retinoblastoma (Rb); apoptosis-inducing factor (AIF); serine/threonine-protein phosphatase 2A (PP2A); B-cell leukemia 2 (Bcl-2); X-linked inhibitor of apoptosis protein (Xiap); human homolog of Drosophila Mad (mothers against decapentaplegic) and related Caenorhabditis elegans gene Sma, family member 1 (Smad1); single-stranded DNA binding protein 2 alpha (SSBP2α); poly(adenosine diphosphate-ribose) polymerase (PARP); GRB2-associated binding protein 2 (Gab2); and tripartite motif containing 24 (Trim24). It is noteworthy that several of these proteins also were overexpressed in the CD34-positive compartment, which putatively contains the CML stem cell population. Conclusions: The results from this study indicated that reverse phase protein array analysis can unveil differentially expressed proteins in advanced phase CML that can be exploited therapeutically with targeted approaches. Cancer 2012.

Original languageEnglish (US)
Pages (from-to)5283-5292
Number of pages10
JournalCancer
Volume118
Issue number21
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

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Protein Array Analysis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Proteomics
Myeloid Progenitor Cells
Protein-Tyrosine Kinases
Leukemia
Proteins
X-Linked Inhibitor of Apoptosis Protein
Smad Proteins
Apoptosis Inducing Factor
B-Cell Leukemia
Poly Adenosine Diphosphate Ribose
Leukemia, Myeloid, Chronic Phase
HSP90 Heat-Shock Proteins
Protein Phosphatase 2
Retinoblastoma
Caenorhabditis elegans
DNA-Binding Proteins
Threonine
Oncogenes

Keywords

  • blastic phase
  • chronic myeloid leukemia
  • chronic phase
  • protein expression
  • proteomics
  • reverse phase protein array
  • signature

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34-positive compartment. / Quintás-Cardama, Alfonso; Qiu, Yi Hua; Post, Sean M.; Zhang, Yiqun; Creighton, Chad J.; Cortes, Jorge; Kornblau, Steven M.

In: Cancer, Vol. 118, No. 21, 01.11.2012, p. 5283-5292.

Research output: Contribution to journalArticle

Quintás-Cardama, Alfonso ; Qiu, Yi Hua ; Post, Sean M. ; Zhang, Yiqun ; Creighton, Chad J. ; Cortes, Jorge ; Kornblau, Steven M. / Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34-positive compartment. In: Cancer. 2012 ; Vol. 118, No. 21. pp. 5283-5292.
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AU - Zhang, Yiqun

AU - Creighton, Chad J.

AU - Cortes, Jorge

AU - Kornblau, Steven M.

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