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p16 gene homozygous deletions in acute lymphoblastic leukemia
B Quesnel, C Preudhomme, N Philippe, M Vanrumbeke, I Dervite, JL Lai, F Bauters, E Wattel and P Fenaux
U124 Inserm Institut de Recherches sur le Cancer, C.H.U. Lille, France.
The p16 protein is a cyclin inhibitor encoded by a gene located in 9p21,
which may have antioncogenic properties, and is inactivated by homozygous
p16 gene deletion or, less often, point mutation in several types of solid
tumors often associated to cytogenetic evidence of 9p21 deletion. We looked
for homozygous deletion and point mutation of the p16 gene in acute
lymphoblastic leukemia (ALL), where 9p21 deletion or rearrangement are also
nonrandom cytogenetic findings. Other hematologic malignancies including
acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic
lymphocytic leukemia (CLL), and myeloma were also studied. Homozygous
deletion of the p16 gene was seen in 9 of the 63 (14%) ALL analyzed,
including 6/39 precursor B-ALL, 3/12 T-ALL, and 0/12 Burkitt's ALL. Three
of the 7 ALL with 9p rearrangement (including 3 of the 5 patients where
this rearrangement was clearly associated to 9p21 monosomy) had homozygous
deletion compared to 5 of the 55 patients with normal 9p (the last patient
with homozygous deletion was not successfully karyotyped). Single stranded
conformation polymorphism analysis of exons 1 and 2 of the p16 gene was
performed in 88 cases of ALL, including the 63 patients analyzed by
Southern blot. Twenty-six of the cases had 9p rearrangement, associated to
9p21 monosomy in at least 12 cases. A missense point mutation, at codon 49
(nucleotide 164), was seen in only 1 of the 88 patients. No homozygous
deletion and no point mutation of the p16 gene was seen in AML, MDS, CLL,
and myeloma. Homozygous deletion of interferon alpha genes (situated close
to p16 gene in 9p21) was seen in only 3 of the 9 ALL patients with p16 gene
homozygous deletion, and none of the ALL without p16 gene homozygous
deletion. Our findings suggest that homozygous deletion of the p16 gene is
seen in about 15% of ALL cases, is not restricted to cases with
cytogenetically detectable 9p deletion, and could have a pathogenetic role
in this malignancy. On the other hand, p16 point mutations are very rare in
ALL, and we found no p16 homozygous deletions or mutations in the other
hematologic malignancies studied.
Volume 85,
Issue 3,
pp. 657-663,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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