CANDIDATE TUMOR-SUPPRESSOR GENES MTS1 (P16(INK4A)) AND MTS2 (P15(INK4B)) DISPLAY FREQUENT HOMOZYGOUS DELETIONS IN PRIMARY-CELLS FROM T-CELL BUT NOT FROM B-CELL LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIAS

Using a Southern blot approach, deletions of MTS1 (multiple tumor-suppressor gene 1) and MTS2 (multiple tumor-suppressor gene 2) candidate tumor-suppressor genes have been studied in primary neoplastic cells from 55 acute lymphoblastic leukemia (ALL) patients, Homozygous MTS1 deletions were found in 20 of 24 T-ALL cases and in only 2 of 31 B-lineage cases (P < .001), The deletions involved MTS1 and MTS2 in most cases, Homozygous MTS2 deletions were observed in 16 of 24 T-ALL cases and in 1 of 31 B-lineage ALLs (P < .001), all of them displaying homozygous MTS1 deletions. In 5 cases (4 T and 1 B), deletions involved MTS1 but spared the MTS2 gene, showing that one deletion breakpoint was located between the two genes within a 25-kb region. In 1 T-ALL case, an MTS1 gene rearrangement has occurred downstream to exon 2, Possible hemizygous deletions were found in 6 cases, 4 of them of the B-cell lineage, In 7 ALL cases, cells obtained at presentation and at first relapse were studied and identical results were observed in 6 cases. In 1 B-lineage case, a germline pattern was found at presentation and a possible monoallelic MTS1/MTSZ deletion was observed at relapse, The high frequency of MTS1 and MTS2 homozygous deletions in T-ALLs supports the view that inactivation of these genes plays an important role in the pathogenesis of this type of human leukemia. (C) 1994 by The American Society of Hematology.