The role of p53 in megakaryocyte differentiation and the megakaryocytic leukemias of Down syndrome

Sequence analysis of the p53 tumor suppressor gene was performed on diagnos tic blood and bone marrow samples from nine children with Down syndrome and acute megakaryoblastic leukemia. p53 sequence alterations were not observe d in any of seven cases of transient leukemia; however, samples from two of three patients with acute megakaryoblastic leukemia harbored sequence alte rations. The acquisition of both mutations (Gly245Val and Arg72Pro) in the transformation from transient leukemia to overt acute megakaryoblastic leuk emia suggests a functional role of mutant p53 in the evolution of this dise ase. (C) Elsevier Science Inc., 1999. All rights reserved.