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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 [see comments]
J Hebert, JM Cayuela, J Berkeley and F Sigaux
Laboratory of Molecular Hematology, Centre Hayem, Hopital Saint Louis,
Paris, France.
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.
Volume 84,
Issue 12,
pp. 4038-4044,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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