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Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34-positive compartment
Version of Record online: 19 APR 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 21, pages 5283–5292, 1 November 2012
How to Cite
Quintás-Cardama, A., Qiu, Y. H., Post, S. M., Zhang, Y., Creighton, C. J., Cortes, J. and Kornblau, S. M. (2012), Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34-positive compartment. Cancer, 118: 5283–5292. doi: 10.1002/cncr.27568
- Issue online: 19 OCT 2012
- Version of Record online: 19 APR 2012
- Manuscript Accepted: 29 FEB 2012
- Manuscript Revised: 23 FEB 2012
- Manuscript Received: 28 DEC 2011
- chronic myeloid leukemia;
- protein expression;
- reverse phase protein array;
- blastic phase;
- chronic phase;
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.
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).
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.
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. © 2012 American Cancer Society.