Abstract
Cytogenetic stratification remains insufficient for almost half of the acute myeloblastic leukemia (AML) cases, with AML patients requiring subsequent molecular investigation. In our study, we used mass spectrometry (MS)-based proteomic approaches to characterize de novo AML. Fifty-four samples (mononuclear cells from bone marrow or peripheral blood mononuclear cells collected and frozen before treatment) from two independent cohorts of newly diagnosed AML patients were analyzed. We showed that the protein signature of leukemic cells defined two clusters that displayed significant variation for overall and disease-free survival (P=0.001 and 0.0004, respectively). This proteomic classification refines the cytogenetic classes. AML patients with intermediate and unfavorable cytogenetic classifications could be subdivided according to their protein profiles into subgroups with significantly different survival rates. Among the proteins expressed by leukemic cells, we isolated a 10 800-Da marker that retained the highest discriminative value between living and deceased patients. The 10 800-Da marker was identified by MS peptide sequencing as S100A8 (also designated MRP8 or calgranulin A). Western blot analysis confirmed its expression mainly in AML patients with the worst prognosis, arguing for a selective deregulation associated with poor prognosis. These results suggest that the expression of S100A8 in leukemic cells is a predictor of low survival.
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Acknowledgements
We thank Professor Polack B (Laboratory of Hemostasis, Grenoble University Hospital) for his help in statistical analysis, Professor Seve M (proteomic platform of Grenoble University Hospital) for access to the MALDI-TOF/TOF MS platform and Coute Y from the Laboratory of Chemical Biochemistry UNIT-M 201 CEA for the nanoLC MS/MS data. This work was supported by grants from the ‘Direction de la recherche clinique-CHU Grenoble, France’ and the ‘Groupe d'étude ouest-est des leucémies: GOELAMS.’
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Nicolas, E., Ramus, C., Berthier, S. et al. Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients. Leukemia 25, 57–65 (2011). https://doi.org/10.1038/leu.2010.251
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DOI: https://doi.org/10.1038/leu.2010.251
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