Depletion of MLL-AF4 fusion gene by RNAi inhibits proliferation and induces apoptosis in t(4;11)-positive SEM cells

The t(4;11)(q21;23) translocation is diagnosed in more than 50% of infant high-risk acute lymphoblastic leukemias and is associated with very poor prognosis. Using RNAi, we have silenced the expression of MLL-AF4 fusion gene in the SEM cells carrying t(4;11)(q21;23) translocation. Down-regulation of MLL-AF4 mRNA expression by specific siRNAs caused more than two-fold transient decrease in mRNA levels, reduced 10-fold the clonogenic capacity of siRNA-treated cells. Two transfections of SEM cells with the MLL-AF4 siRNAs also reduced the proliferation, inhibited G1-S transition in cell cycle and induced apoptosis.…