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August 1997, Volume 11, Number 8, Pages 1187-1192
Table of contents    Previous  Abstract  Next   Article  PDF
Rapid communication
Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60
J Zavadil1, J Bezinová1, P Svoboda1, Z Zemanová2 and K Michalová1,2

1Institute of Hematology and Blood Transfusion, Prague, Czech Republic

2Third Medical Department, First Medical Faculty, Charles University, Prague, Czech Republic

Abstract

Deletions of the long arm of chromosome 5 with common overlapping segment 5q31.1 are among the most frequent cytogenetic aberrations in myelodysplastic syndromes and acute myeloid leukemias (MDS/AML). We have constructed a YAC-based physical map of the 5q31.1 critical locus and localized the transcriptional transactivator Smad5 adjacent to loci showing consistent loss of heterozygosity in these disorders. Smad5 plays a key role along the bone morphogenetic protein-4 (BMP-4) inhibitory signalling pathway inducing embryonic hematopoiesis. Smad5 homologs Smad2 and DPC4 have recently been linked to human cancer. FISH analysis of AML-M2 cell line HL60 and of four MDS/AML patients revealed consistent hemizygous loss of the Smad5 locus. In HL60 cells, a translocation event within 5q31.1 associated with loss of adjacent material leads to disruption of the critical locus with partial retention of the 5q31.1 genomic sequences on a marker chromosome. RT-PCR sequencing analysis of the HL60 Smad5 remaining allele ruled out the functional inactivation of the gene analogous to that occurring in the Smad5 homologs DPC4 and Smad2 in cases of pancreatic and colorectal cancers. Mutational analysis of Smad5 in MDS/AML cases is in progress.

Keywords

myeloid leukemia/etiology; chromosome 5q; human; gene mapping; fluorescent in situ hybridization; gene mutation

Received 14 February 1997; accepted 21 April 1997
August 1997, Volume 11, Number 8, Pages 1187-1192
Table of contents    Previous  Abstract  Next   Article  PDF