MLL-AF4 oncoprotein up-regulates fibroblast growth factor receptor 2 (FGFR2) gene expression in hematopoietic progenitor cells

Mixed lineage leukemia (MLL) gene rearrangements are frequent in childhood acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) translocation fuses the 5′ portion of MLL to the 3′ portion of AF4 and leads to the synthesis of a chimeric MLL-AF4 oncoprotein. MLL-AF4 miss-regulates the expression of MLL target genes, which are implicated in cell differentiation and proliferation (HoxA9, Meis1, p27kip1) (1,2). High risk t(4;11)(q21;q23) ALL originates in primitive lymphoid-restricted CD34+CD19- cells, thus supporting the hypothesis that the poor outcome is a consequence of primitive stem cell transformation (3). We used CD34+ hematopoietic stem and precursor cells isolated from human cord-blood, to identify MLL-AF4 early target genes. Purified cells were transfected with p3XFlag/MLL-AF4 construct and total RNA was extracted. Real-Time RT-PCR preliminary data show that transcription levels of FGFR2, a nuclear molecular partner of AF4 and MLL-AF4 proteins, increases in MLL-AF4-expressing CD34+ progenitors