HOMOZYGOUS DELETIONS OF THE P15 (MTS2) AND P16 (CDKN2/MTS1) GENES IN ADULT T-CELL LEUKEMIA

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type I (HTLV-I), Twenty to 40 years often elapse from viral infection to overt ATL, suggesting that other genetic events must occur to produce frank leukemia. The p15 (MTS2) and pie (CDKN2/MTS1) genes located on chromosome 9p have been implicated as candidate tumor-suppressor genes in several types of tumors. We examined for alterations of these genes in ATL using Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. Both p15 and p16 genes were homozygously deleted in 4 of 23 acute/lymphomatous ATL (17%). An additional 3 (13%) and 4 (17%) acute/lymphomatous samples had hemizygous deletions in at least one exon of p15 and p16, respectively. One of 14 chronic ATL samples had a homozygously deleted p16 gene and another had a hemizygous deletion of p16, Neither homozygous nor hemizygous deletions of the p15 gene were found in chronic ATL, In total, 10 of 37 (27%) ATL samples had loss of the p15 and/or p16 genes. No point mutations of the p15 and pie genes were found. The ATL patient with a homozygously deleted pie in the chronic phase rapidly progressed to acute ATL and died within 6 months of the initial diagnosis. One instructive patient had no detectable deletion of the p15 and p16 genes during the chronic phase of ATL but had a homozygous deletions of both genes when she progressed to acute ATL, Our results suggest an association of p15/p16 deletions with development of acute ATL. (C) 1995 by The American Society of Hematology,