THE METHYLTHIOADENOSINE PHOSPHORYLASE GENE IS FREQUENTLY CO-DELETED WITH THE P16(INK4-ALPHA) GENE IN ACUTE TYPE ADULT T-CELL LEUKEMIA

Adult T-cell leukemia (ATL) is a retrovirus-associated leukemia with p oor prognosis and often has deletions of the p16(INK4a) and p15(INK4b) genes on chromosome 9p21. The gene for methylthioadenosine phosphoryl ase (MTAP), a purine and methionine metabolic enzyme, resides approxim ately 100 Kb telomeric to the p16(INK4a) gene and is frequently co-del eted with the tumor suppressor gene in a variety of cancers. This enzy me deficiency can be exploited for selective chemotherapy with de novo purine synthesis inhibitors and/or methionine depletion. To determine whether ATL can be a candidate for selective chemotherapy based on ge netic alterations on chromosome 9p21, we analyzed the MTAP gene in 41 samples from ATL patients (27 acute type and 14 chronic type ATL) and 3 cell lines established from ATL patients. Five samples from the acut e type had deletions of the MTAP gene (4 total deletions and 1 partial deletion of exons 6-8). The MTAP gene was always co-deleted with P16( INK4a). No deletion of the MTAP gene was detected in samples from the chronic type. Of 3 cell lines, 2 showed partial deletions of exons 5-8 of the MTAP gene, and 1 lost all exons. The p16(INK4a) gene was delet ed in all cell lines. In conclusion, deletions of the MTAP gene were f ound in 5 of 27 acute type ATL samples. Acute type ATL with MTAP defic iency can be a good candidate for selective chemotherapy by depleting purines and/or methionine. (C) 1998 Wiley-Liss, Inc.