A new type of p16INK4/MTS1 gene transcript expressed in B-cell malignancies

Chromosome band 9p21-22 is frequently altered by nonrandom abnormalities, mainly deletions, in hemopoietic malignancies of the lymphoid lineage. We have analysed a translocation t(9;14)(p21-p22;q11) in a B-cell type acute lymphoblastic leukemia. Location of the 14q11 breakpoint within the TCR-alpha/delta locus allowed the isolation of a fusion transcript composed of a 3' segment containing part of the constant region of the TCR-alpha gene and a 5' segment from chromosome 9, designated 0.18. This 0.18 segment was also part of cDNAs isolated from two tumoral B-cell lines (RPMI-8226, Raji). In both cases, 0.18 was juxtaposed 5' to a sequence corresponding to exons 2 and 3 of the p16INK4/MTS1 gene which is located on band 9p21-22. Unexpectedly, none of the two ATG codons found in 0.18 was in phase with that of the exons 2 and 3 of p16INK4/MTS1. Furthermore, in vitro translation product of a RPMI-8226 cDNA clone generated a product that was not immunoprecipitated by antibodies specific of the C-terminal end of the p16INK4/MTS1 protein. Evidence for similar transcripts in non tumoral lymphoid B cells (unstimulated peripheral blood lymphocytes (PBL) and lymphoblastoid cell lines) were obtained by using amplimers representative of the 0.18 segment and the p16INK4/MTS1 exon 2. Altogether, these data are consistent with the existence of a new type of p16INK4/MTS1 transcript whose significance is discussed.