Study of Bone Marrow Samples From Patients With Acute Leukemia

Leukemia

adult acute megakaryoblastic leukemia (M7)

RATIONALE: Studying the genes expressed in samples of bone marrow from patients with cancer may help doctors identify biomarkers related to cancer. PURPOSE: This research study is looking at bone marrow samples from patients with acute leukemia.

OBJECTIVES: * To perform high throughput sequencing of a set of megakaryocyte specific transcription factors, tyrosine kinases, and Src kinases in DNA isolated from bone marrow specimens of adults with acute megakaryoblastic leukemia (AMKL). * To assay the ability of Src kinase inhibitors (SU6656, dasatinib) to induce differentiation of AMKL blasts in these patients. OUTLINE: DNA from previously collected bone marrow samples are sequenced to analyze genes associated with transcription factors (GATA1, GATA2, SCL, FOG-1, ETS1, ETS2, ERG, FLI-1, GABP, HOXA11, NF-E2, and RUNX1), tyrosine kinases (JAK2, JAK3, and c-MPL), and Src family kinases (LYN, FYN, and HCK) and compared with control DNA. Using bioinformatics, gene alterations are compared to known polymorphisms and subsequent changes in the amino acid sequence of the encoded protein. Subsequent assays assess the effect on proliferation and differentiation and in vitro studies evaluate the consequences of mutations on transcription factor and kinase activity abilities. The effect of SU6656 and dasatinib on cell death and polyploidization is evaluated by flow cytometry and compared with control DNA.

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