Mf. Faienza et al., P16(INK4A) GENE HOMOZYGOUS DELETIONS IN HUMAN ACUTE LEUKEMIAS WITH ALTERATIONS OF CHROMOSOME-9, British Journal of Haematology, 93(3), 1996, pp. 632-636
Acute leukaemias are characterized by non-random chromosomal aberratio
ns which are often strictly related to the inactivation of tumour supp
ressor genes (TSGs). Alterations at the short arm of chromosome 9 have
been reported in a remarkable percentage of acute lymphoblastic leuka
emias (ALL) and have been suggested to cause the loss of activity of t
he putative TSG, p16(INK4A) (MTS1/CDKN2) gene. In order to evaluate th
e correlation between this gene inactivation and visible cytogenetic a
bnormalities, we have investigated p16(INK4A) homozygous gene deletion
s in 10 paediatric acute leukaemias of different cell lineages which d
emonstrated karyotype aberrations involving chromosome 9. Moreover, th
e dimension of the genetic alteration was evaluated by studying the lo
ss of heterozygosity of two highly polymorphic markers of chromosome 9
p, namely alpha-interferon (IFNA) and D9S104, and the deletion of 5'-m
ethylthioadenosine phosphorylase (MTA-Pase) gene. Finally, the deletio
n of a gene belonging to p16(INK4A) family, the p18 gene, was analysed
in these acute leukaemias. Our results demonstrated that: (i) the bia
llelic loss of p16(INK4A) gene is strictly related to a specific immun
ophenotype, namely ALL of T-cell lineage; (ii) no significant correlat
ion exists between alterations at chromosome 9p level and the homozygo
us deletions of p16(INK4A) gene: and (iii) p18 gene was not deleted in
the examined cases. These findings suggest a possible correlation bet
ween the T-lymphocyte phenotype and tile expression of p16(INK4A) gene
. Moreover, the absence of MTAPase activity seems to be a valuable mar
ker of p(INK4A) gene inactivation, thus indicating that the deleted ch
romosomal area on 9p21 very frequently involves the MTAPase gene.