Candidate tumor-suppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T- 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/MTS2 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.
Hebert
J
J
Laboratory of Molecular Hematology, Centre Hayem, Hopital Saint Louis, Paris, France.
Cayuela
J M
JM
Berkeley
J
J
Sigaux
F
F
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D007963:Leukocytes, Mononuclear; D008875:Middle Aged; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells; D017384:Sequence Deletion
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm