Mitochondrial dysfunction has been associated with chronic degenerative diseases, aging and cancer. Mitochondrial proteins are interesting targets for the study of apoptosis in leukemia and other malignancies. Modern mass-spectrometry instrumentation has achieved excellent performance in terms of sensitivity, resolution and mass accuracy; however, so far, the contribution of proteomics to the care of patients with AML is virtually zero. Therefore, we set up strategies for the proteomic analysis of the mitochondria enriched cytoplasmic fractions in primary AML cells. Primary AML cells and normal blood cells were derived from bone marrow aspirates of a group of five patients with AML (M1 and M2) at the time of initial diagnosis before chemotherapy and three healthy controls. Peptide mass spectra were obtained on a MALDI-TOF-TOF mass spectrometer. Protein identification was processed and analyzed by searching the Swiss-Prot protein database using the MASCOT search engine of Matrix Science that integrated in the Global ProteinServer Workstation. Tandem electrospray ionization mass spectrometry (ESI-MS/MS) experiments were performed on a quadrupole (Q)-time of flight 2 (Q-TOF2) hybrid quadrupole/TOF mass spectrometry. We identified 48 spots corresponding to 38 proteins in primary AML cells, the expressions of which were altered significantly compared with normal blood cells. Out of these deregulated proteins, totally 12 and 20 proteins were observed in up- or down-regulated spots, respectively. Interestingly, prohibitin (gi4505773) was highly expressed in primary AML cells. Prohibitin is known to induce growth suppression and repress E2F-mediated transcription. But it has recently found that prohibitin protects cells from apoptosis by down-regulating E2F activity when Rb family members are inactive (
Disclosure: No relevant conflicts of interest to declare.