17p Deletion in acute myeloid leukemia and myelodysplastic syndrome. Analysis of breakpoints and deleted segments by fluorescence in situ.
Recently, we and other groups reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) a strong correlation between cytogenetic rearrangements leading to 17p deletion, a typical form of dysgranulopoiesis combining pseudo-Pelger-Huët hypolobulation and small vacuoles in neutrophils, and p53 mutation. To gain further insight into this "17p-syndrome," we studied 17 cases of AML and MDS with 17p deletion by whole chromosome painting (WCP) and fluorescence in situ hybridization (FISH) with probes spanning the 17p arm, including a p53 gene probe. Cytogenetically, 15 patients had unbalanced translocation between chromosome 17 and another chromosome (chromosome 5 in nine cases and unidentified chromosome -add 17p- in three cases), one patient had monosomy 17, and one had i(17q). All rearrangements appeared to result in 17p deletion. Sixteen patients had additional cytogenetic rearrangements. WCP analysis confirmed the cytogenetic interpretation in all cases and identified one of the cases of add 17p as a t(17;22). WCP also identified chromosome 17 material on a marker or ring chromosome in two cases of t(5;17). FISH analysis with 17p markers made in 16 cases showed no deletion of the 17p markers studied in the last two patients, who had no typical dysgranulopoiesis; p53 mutation analysis in one of them was negative. In the 14 other cases, FISH showed a 17p deletion of variable extent but that always included deletion of the p53 gene. All 14 patients had typical dysgranulopoiesis, and all but one had p53 mutation and/or overexpression. These findings reinforce the morphologic, cytogenetic, and molecular correlation found in the 17p-syndrome and suggest a pathogenetic role for inactivation of tumor suppressor gene(s) located in 17p, especially the p53 gene.
Soenen
V
V
Laboratoire d'Hématologie, Service de Cytogénétique, Lille, France.
Preudhomme
C
C
Roumier
C
C
Daudignon
A
A
Laï
J L
JL
Fenaux
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002871:Chromosome Banding; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D014178:Translocation, Genetic