HSH2D contributes to methotrexate resistance in human T-cell acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is a malignant proliferative disease that originates from B-lineage or T-lineage lymphoid progenitor cells. Resistance to chemotherapy remains an important factor for treatment failure. The aim of the present study was to investigate drug resistance in T-cell ALL (T-ALL). Bioinformatics analysis of Oncomine and Gene Expression Omnibus data was performed to evaluate the expression of haematopoietic SH2 domain containing (HSH2D) in various lymphomas. HuT-78 cells with HSH2D overexpression and or knockdown were constructed, and the effect on related downstream signalling molecules was detected. To study the effect of HSH2D on methotrexate (MTX) resistance, cell cycle and apoptosis analyses were conducted using flow cytometry, and MTT and EdU assays were used to detect the effect of MTX resistance and HSH2D gene expression on the biological function of HuT-78 cells. Via the analysis of the data sets, it was identified that the expression of HSH2D was downregulated in T-ALL compared with B-cell ALL. Western blotting and reverse transcription-quantitative PCR demonstrated that the overexpression of HSH2 resulted in the inhibition of CD28-mediated IL-2 activation. In related experiments with drug-resistant cell lines, it was determined that HSH2D expression is necessary for HuT-78 cells to be resistant to MTX. In conclusion, the results suggested that HSH2D serves an important role in the resistance of T-ALL to MTX, which provides a potential research target for the study of drug resistance of T-ALL.