Identification of Potential Oncogenes on Chromosome 21 by RNA Interference Screening

Children with Down syndrome (DS) have an increased risk to develop acute megakaryoblastic leukemia (AMKL). Acquired mutations in the hematopoietic transcription factor GATA1 are consistently present in DS-AMKL, but are insufficient to induce leukemia in the absence of trisomy 21. To identify genes on chromosome 21 which have the potential to contribute to leukemogenesis, we conducted a lentiviral shRNA screening in leukemic cell lines (CMK, CMY [DS-AMKL], M-07 [non DS-AMKL], K562 [erythroleukemia]) and used coexpressed GFP to evaluate cell proliferation by flow cytometry. Using this approach we could identify th…