Genetic analysis of chromosome 13 deletions in BCR/ABL negative chronic myeloproliferative disorders

Chromosomal deletions of band 13q14 occur recurrently in BCR/ABL negative chronic myeloproliferative disorders (CMPD), including myelosclerosis with myeloid metaplasia (MMM), polycythemia vera (PV), essential thrombocythemia (ET), juvenile chronic myeloid leukemia (JCML), and the so‐called BCR/ABL ⁻ chronic myeloid leukemia (CML). The RB1 tumor suppressor locus, mapping to 13q14, has long since been hypothesized as the important gene. In this report, we have determined the frequency of 13q14 deletions at the molecular level in a large panel of BCR/ABL ⁻ CMPD at different disease stages and performed a detailed genetic analysis of gross rearrangements/deletions and point mutations of the RBI gene in these disorders. Our data show that molecular deletions of 13q14 are detected in a relatively large fraction of BCR/ABL ⁻ CMPD (38%), that they appear to be more frequent in MMM than in other BCR/ABL ⁻ CMPD, and that they may be present at diagnosis or occur during blastic evolution of the neoplasia. The RBI gene displayed a germline configuration in all BCR/ABL ⁻ CMPD tested, suggesting that 13q14 deletions in these disorders affect a tumor suppressor locus distinct from RB1.