The incidence of chromosome 9p21 abnormalities and deletions of tumor suppressor genes p15(INK4b)/p16(INK4a)/p14(ARF) in patients with acute lymphoblastic leukemia

Cytogenetic changes are of pivotal prognostic significance in patients with de novo acute lymphoblastic leukemia (ALL). However, in some cases leukemi c blasts can harbor gene lesions on a submicroscopic level without evidence of a corresponding abnormality by conventional cytogenetic studies. This c an result in failure to recognize chromosomal abnormalities and inappropria te evaluation with respect to therapy assignments. To study the discrepancy in the detection of deletions of the short arm of chromosome 9 and deletio ns of tumor suppressor genes p15/p16/p14 on chromosome 9p21, we analyzed bo ne marrow samples from 92 patients with ALL both by cytogenetic analysis an d by Southern blot. In 41 patients (45%), we found deletions of p15/p16/p14 , which were homozygous in 27 and hemizygous in 14. Cytogenetic analysis de monstrated abnormalities of the short arm of chromosome 9 in the form of 9p - or del(9p21-22) in only 5 of the 41 patients (12%). Only 2 of 51 patients without gene deletions as detected by Southern blot revealed a 9p- abnorma lity, which was found only in a subpopulation of the cells. We demonstrate that deletions of the p15/p16/p14 genes on chromosome 9p21 are more frequen t than indicated by cytogenetic analysis. Molecular techniques in addition to cytogenetic studies are necessary to detect otherwise-unrecognized genet ic lesions of the short arm of chromosome 9.