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 cytog enetic rearrangements leading to 17p deletion, a typical form of dysgr anulopoiesis combining pseudo-Pelger-Huet hypolobulation and small vac uoles in neutrophils, and p53 mutation. To gain further insight into t his ''17p-syndrome,'' we studied 17 cases of AML and MDS with 17p dele tion by whole chromosome painting (WCP) and fluorescence in situ hybri dization (FISH) with probes spanning the 17p arm, including a p53 gene probe. Cytogenetically, 15 patients had unbalanced translocation betw een chromosome 17 and another chromosome (chromosome 5 in nine cases a nd unidentified chromosome -add 17p-in three cases), one patient had m onosomy 17, and one had i(17q). All rearrangements appeared to result in 17p deletion. Sixteen patients had additional cytogenetic rearrange ments. WCP analysis confirmed the cytogenetic interpretation in all ca ses 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 t wo cases of t(5;17). FISH analysis with 17p markers made in 16 cases s howed 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 morpholo gic, cytogenetic, and molecular correlation found in the 17p-syndrome and suggest a pathogenetic role for inactivation of tumor suppressor g ene(s) located in 17p, especially the p53 gene. (C) 1998 by The Americ an Society of Hematology.