Pretreatment bone marrow samples from 46 newly diagnosed acute myeloid leukemia (AML) patients were analyzed by qRT-PCR. The aim of the present study was to evaluate mRNA expression of RUNX1,2 and 3 along with the hedgehog ligands Indian hedgehog(IHH) and Sonic hedgehog (SHH) and correlated their expressions with various clinicopathological parameters in adult human Egyptian (AML) patients. AML patients had significantly increased expression of RUNX1 & RUNX2 and significantly decreased expression of the Hedgehog ligands (IHH&SHH) compared to normal bone marrow samples.
Spearman Correlation Coefficient test showed positive correlation of RUNX3 gene expression with platelet count, but a significant negative correlation with total leukocytic count and peripheral blood blasts. This reduced circulating tumor burden induced by RUNX3 overexpression, was not significantly reflected upon complete remission induction. But was clearly manifested by a significantly improved overall survival (P=0.015) on univariate analysis. Multivariate analysis showed that higher expression of RUNX3 & increased hemoglobin level were the only independent factors which affect OS significantly. This significant effect was not achieved by any of the other four studied genes.
Ectopic co-expression of the hedgehog ligands: Indian hedgehog (IHH) & Sonic hedgehog (SHH) in AML was observed. No significant correlation between RUNX3expression & either IHH or SHH was observed. The link between HH pathway & RUNXs family members was provided by a significant positive correlation between RUNX2& IHH. In conclusion, RUNX3 over expression is a good prognostic factor in Egyptian adult non-M3 AML.