The pathogenic role of MEF2D-SS18 fusion gene in B-cell acute lymphoblastic leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by various fusion genes resulted from chromosome translocations, and MEF2D related fusions are recently identified in a B-ALL subtype with relatively worse survival. In this study, we investigated the pathogenic role of MEF2D-SS18 fusion in B-ALL. The recombinant retrovirus and lentivirus plasmids containing the MEF2D-SS18 transcript were constructed for functional studies. Immuno-fluorescent staining presented the nuclear localization of MEF2D-SS18. In vitro B cell differentiation assay showed MEF2D-SS18 significantly inhibited the differentiation of mouse common lymphoid progenitors into CD19 positive B cells. The data of RBMT mouse model also showed B cell developmental arrest. In REH cells overexpressing MEF2D-SS18, genes related to B cell development were down-regulated, while genes related to drug sensitivity and B cell survival were up-regulated. In conclusion, MEF2D-SS18 fusion gene blocked the differentiation of B cells, thus exerted a funding role in the pathogenesis and prognosis of B-ALL.