Overexpression of HHEX in Acute Myeloid Leukemia with t(8;21)(q22;q22) Translocation.

BACKGROUND:The hematopoietically expressed homeobox (HHEX) is widely expressed in hematopoietic stem cells and is an essential transcription factor in embryonic development; however its role in hematopoiesis and leukemogenesis is poorly understood. We are thus exploring the association of HHEX and acute myeloid leukemia (AML). METHODS:The study included 56 AML patients and 12 normal bone marrows (NBMs). Real-time quantitative polymerase chain reaction (Q-PCR) was used to assess HHEX expression. The functional consequences of this gene were explored in the Kasumi-1 cell-line following dampened expression of HHEX. This was done by transfecting small interfering RNA (siRNA). RESULTS:Expression levels of HHEX in AML were similar to that found in controls (0.094±0.103 vs. 0.078±0.112; p=0.203), but AML with t(8;21) was more prevalent than other types of AMLs (p<0.01) or controls (p<0.05). Expression levels of HHEX in AML (non-M3) did not significantly affect overall survival (p=0.555). In vitro studies carried out in Kasumi-1 cells suggest that after decreasing HHEX, cell viability at 48 and 72 h were significantly reduced compared to controls (p<0.05). The apoptotic rate was also significantly increased at 48 and 72 h compared to controls (p<0.05). CONCLUSIONS:HHEX is expressed in multiple types of AML, with the highest levels seen in t(8;21) AML. HHEX was essential for Kasumi-1 cell proliferation and may represent a potential therapeutic target enabling against AML.

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