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Detection of homozygous deletions of the cyclin-dependent kinase 4
inhibitor (p16) gene in acute lymphoblastic leukemia and association with
adverse prognostic features
M Fizzotti, G Cimino, S Pisegna, G Alimena, C Quartarone, F Mandelli, PG Pelicci and F Lo Coco
Department of Human Biopathology, University La Sapienza of Roma, Italy.
A recently described putative tumor suppressor gene, the cyclin- dependent
kinase 4 inhibitor (p16), has been shown to be altered by deletions and/or
point mutations in various human cancers. To assess the incidence and
clinico-biologic correlations of p16 homozygous deletion in hemopoietic
tumors, we studied a panel of 244 DNA samples representative of distinct
acute (99 cases) and chronic (57 cases) leukemia subtypes, myelodysplastic
(22 cases) and myeloproliferative (15 cases) syndromes, and lymphomas (51
cases). A 361-bp probe complementary to the p16 exon 2 gene sequences was
generated by polymerase chain reaction and used in Southern blot
hybridization against these tumor DNAs. Homozygous deletions of p16
(p16-/-) were detected in 10 of 58 (17%) cases of acute lymphoblastic
leukemia (ALL) of either B or T lineage and in no other tumors.
Single-strand conformation polymorphism analysis of p16 exons 1 and 2 was
also performed in 40 of the 58 ALL cases and in 16 lymphomas. In no cases
were point mutations detected. The comparison of clinical features at
presentation in p16-/- and in p16 germline ALL cases showed a greater
leukemic cell mass (P = .001) and higher white blood cell counts (P = .01)
in the former group. Two ALL cases in which diagnostic and relapse DNA
samples were available showed p16-/- in both specimens. We conclude that
homozygous p16 gene deletions characterize a subset of ALL with features of
aggressive disease.
Volume 85,
Issue 10,
pp. 2685-2690,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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