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

Blood. 2000 Mar 15;95(6):2138-43.


Nonrandom interstitial deletions and monosomy of chromosomes 5, 7, and 17 in refractory myelodysplasia (MDS) and acute myelogenous leukemia (AML) suggest a multistep pathway that culminates in aggressive clinical course. Because cytogenetic studies frequently identify chromosome 5 and 17 deletions within a single clone, we searched for allele loss for 5q loci and TP53 gene mutations in the same leukemic samples. Cosegregating deletions of chromosomes 5 and 17 were found to specifically include the 5q13.3 interval between 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 sequence of genetic alterations. Serial molecular analysis of this patient revealed a dysplastic clone with der(5;17), which gave rise to a leukemic clone on acquiring an inactivating mutation of TP53. Our findings are consistent with 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. (Blood. 2000;95:2138-2143)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Anemia, Refractory, with Excess of Blasts / genetics
  • Chromosome Deletion*
  • Chromosomes, Artificial, Yeast
  • Chromosomes, Human, Pair 17*
  • Chromosomes, Human, Pair 5*
  • Contig Mapping
  • Genes, p53 / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / genetics*
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Mutation
  • Myelodysplastic Syndromes / genetics*
  • Physical Chromosome Mapping
  • Tumor Cells, Cultured