Proteome analysis of acute myelogenous leukemia (AML). Molecular mechanisms of cell death regul. in AML rel. to cytogenetics and prognosis.

The malignant hematological disease acute myelogenous leukemia (AML) has an overall long-term survival of 50%, with far worse outcomes in patients over 60 years of age. AML material >90% pure will be collected from patients, before chemotherapy, during c hemotherapy and at disease relapse. Kryopreserved material will be available locally and through the National Leukemia Registry. AML patients will be divided in three groups: a) Standard risk patients wild type Flt3 and normal karyotype, b) unfavorable prognosis (Flt3-ITD, c) favorable prognosis (inversion of chromosome 16). As many as 50% of the AML patients are without known mutations, and a search for molecular alterations in these cases will be emphasized. AML cell extract will be examined by the u se of broad pI an ultrazoome pI for mapping of proteins by 2-dimensional polyacrylamide gel electrophoresis. Protein maps and identifications of the proteins will be correlated to expression analysis in 40k DNA array. Gels are staine d by fluorescent protein stain, and protein spots are excised for mass-spectroscopic examination. A special focus will be on regulation of apoptosis in relation to therapy response and mutations. Functional studies in differentiation and apoptosis will be used to explore the role of the molecules detected.