MOLECULAR ANALYSIS OF THE CYCLIN-DEPENDENT KINASE INHIBITOR GENES, P15, P16, P18 AND P19 IN THE MYELODYSPLASTIC SYNDROMES

The myelodysplastic syndromes (MDS) are a heterogeneous group of clona l blood disorders characterized by dyshematopoiesis with a frequent ev olution to acute leukemia. Chromosomal deletions rather than transloca tions are the predominant karyotypic abnormalities in MDS, suggesting a recessive mechanism in the pathogenesis of MDS, such as inactivation of tumor suppressor genes. A group of cyclin-dependent kinase inhibit ors, p15 (INK4B), p16 (INK4A), p18 (INK4C) and p19 (INK4D), are candid ate tumor suppressor genes. To determine whether genetic alterations o f these genes play an important role in the development and/or progres sion of MDS, we examined 46 samples from MDS patients by Southern blot ting, single-strand-conformation polymorphism (SSCP) using polymerase chain reaction (PCR) and sequencing of DNA. These samples included 13 refractory anemias (RA), four refractory anemias with ringed siderobla sts (RARS), 16 refractory anemias with an excess of blasts (RAEB), eig ht refractory anemias with an excess of blasts in transformation (RAEB -T) and five chronic myelomonocytic leukemia (CMMoL) samples. Except f or allelic polymorph isms or silent point mutations, no alterations of coding regions of these four CDKI genes were identified. In summary, genetic abnormalities of the p15, p16, p18 and p19 genes are rare even ts in the development and/or progression of MDS. (C) 1997 Elsevier Sci ence Ltd. All rights reserved.