TGF-b and TGF-bRII Fluctuation in HLA-DR Negative AML Patients

Acute myeloblastic leukemia is the most frequent cancer in adults and the patients have a wide range of subclasses. HLA DR negative cases represent one of the major immunephenotypic classes. HLADR is routinely used to distinguish acute promyelocytic leukemia (APL) from other AML subclasses based on the immunophenotype. The TGFb signaling pathway, as a critical regulator, guides different vital and sometimes opposite aspects of cell processes, including cell proliferation, apoptosis, differentiation quiescence, and malignancy expansion. A review of previous studies regarding the role of TGFb in human malignancies made us interested in the evaluation of the role of the TGF signaling pathway in leukemia. We evaluated TGFb /TGFbRII fluctuant in ldquo HLADR negative AMLrdquo , at expression level in bone marrow and peripheral blood sles. Fortysix patients were consecutively diagnosed with HLADR negative AML by flow cytometry, morphology, cytochemistry, and molecular analysis. By using Ficoll density centrifugation, mononuclear cells were isolated from the peripheral blood and bone marrow from both patients and controls then, TGFb, TGFbRII, and ABL1 genes were lified by quantitative Real Time PCR. The results revealed that the TGFb expression level was not different between patients and controls while TGFb R was higher in patients than control cases the expression of TGFb and TGFbRII was significantly lower in non M3AML (M0, M1, M2) than M3AML (APL) (P<0.05). We conclude that despite the conventional role of the TGFb/TGFbRII pathway to induce quiescence, anther role was defined for leukemic cells expansion in HLADR negative AML. Currently we are studying this pathway to find the downstream target of leukemogenesis activity.