Molecular Genetic Studies of the Expression Profiling of some Genes Related to Acute Myeloid Leukemia in Adult Patients

Abstract

Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy , It is more common in adults than in children with median age 67 years and it affects men more than women. It has the larg¬est number of annual deaths among leukemias. RUNX family members are DNA-binding transcription factors that play an essential role in developmental cellular processes. They are involved in diverse signaling pathways and play a paradoxical role in tumerigenesis. RUNX genes contribute to hematopoiesis and are frequently implicated in hematologic malignancies. HEDGEHOG(HH) signaling pathway is considered as one of the major developmental pathways which interact with RUNX family and They play an important role in stem-cell biology and malignant transformation. Accordingly, in the present study the expression level and prognostic impact of RUNX family and Hedgehog genes were investigated in acute myeloid leukemia (AML). Correlations of gene expressions with various clinicopathological parameters were studied. Samples were collected from bone marrow of 46 adult AML patients and five normal individuals. Reverse transcriptase quantitative polymerase chain reaction was used to evaluate the expression levels of RUNX family members along with Indian Hedgehog(IHH) and Sonic Hedgehog (SHH).Our results revealed overexpression of RUNX family genes on the other hand downregulation of IHH and SHH comparing with normal control. IHH was positively correlated with SHH and RUNX2 (P<0.001 and P=0.038). RUNX3 was positively correlated with RUNX1(R=0.302,P = 0.042) and platelets (PLT) (R=0.317,P=0.032). IHH,SHH and RUNX2 were inversely associated with CD4 expression on AML blasts (P=0.017, P=0.074 and P=0.011) respectively. RUNX3 was negatively associated with total leukocytic count (TLC) and peripheral blood blast PB Blasts (P=0.005,P=0.001)respectively.RUNX3,IHH and SHH expression were significantly increased with advanced age