Deletions of chromosome 5q13.3 and 17p loci cooperate in myeloid neoplasms

Nonrandom interstitial deletions and monosomy of chromosomes 5, 7, and 17 i n refractory myelodysplasia (MDS) and acute myelogenous leukemia (AML) sugg est a multistep pathway that culminates in aggressive clinical course. Beca use cytogenetic studies frequently identify chromosome 5 and 17 deletions w ithin a single clone, we searched for allele loss for 5q loci and TP53 gene mutations in the same leukemic samples. Cosegregating deletions of chromos omes 5 and 17 were found to specifically include the 5q13,3 interval betwee n the loci D5S672 and D5S620/D5S626, a locus hypothesized to harbor a tumor suppressor gene(1) and the TP53 gene on 17p. A rare patient with secondary refractory MDS and an unbalanced translocation [der(5;17)], which resulted in deletions of the 5q13,3-qter and 17p loci, provided clues on the sequen ce of genetic alterations. Serial molecular analysis of this patient reveal ed a dysplastic clone with der(5;17), which gave rise to a leukemic clone o n acquiring an Inactivating mutation of TP53. Our findings are consistent w ith functional cooperation between a putative tumor suppressor gene at 5q13 .3 that contributes toward the progression of early stages of MDS, and the TP53 gene when mutated, causes transformation to AML. (C) 2000 by The Ameri can Society of Hematology.