ALTERATIONS OF THE CYCLIN-DEPENDENT KINASE INHIBITOR P19(INK4D) IS RARE IN HEMATOPOIETIC MALIGNANCIES

Cyclin-dependent kinase inhibitors (CDKIs) can be classified into two groups based on the structure of the proteins. One group includes the p21 (CIP1, WAF1, CAP20), p27 (Kip1), and p57 (Kip2) CDKIs, which conta in a homologous amino-terminal cyclin-dependent kinase (cdk) inhibitor y domain. The p16 (INK4A), p15 (INK4B), and p18 (INK4C) CDKIs, which h ave an ankyrin repeat motifs, belong to the other group. The p16 and p 15 CDKI genes are very frequently altered in a variety of cancers incl uding hematopoietic malignancies. The pig (INK4D) gene is a newly clon ed CDKI which belongs to the latter group. To determine if p19 genetic alterations play a role in hematopoietic malignancies, we examined DN A from 45 childhood newly diagnosed acute lymphocytic leukemias (ALLs) , 30 acute myeloblastic leukemias (AMLs), 10 chronic myelocytic leukem ias (CMLs), 45 adult T cell leukemias (ATLs), 70 non-Hodgkin's lymphom as (NHLs), and 20 multiple myelomas (MM) as well as 14 ALL, 20 AML, tw o ATL, and five lymphoma cell lines. Using Southern blot analysis, one homozygous deletion of the p19 gene was detected in a human immunodef iciency virus (HIV)-related Burkitt-like lymphoma sample. No point mut ations in any of the samples were found by polymerase chain reaction-s ingle strand conformation polymorphism (PCR-SSCP) analysis. Our invest igation suggests that alterations of p19 do not play an important role in the development of most hematopoietic malignancies.