CHROMOSOME BAND 1P36 CONTAINS A PUTATIVE TUMOR-SUPPRESSOR GENE IMPORTANT IN THE EVOLUTION OF CHRONIC MYELOCYTIC-LEUKEMIA

Chronic myelocytic leukemia (CML) is a common neoplasm of hematopoieti c pluripotent stem cells. Although the evolution from chronic phase to blast crisis (BC) in CML patients is an inevitable clinical feature, little is understood about the mechanisms responsible for the transfor mation. We have previously performed allelotype analysis in CML BC and have detected frequent loss of heterozygosity (LOH) on the short arm of chromosome 1. To know the common region of LOH where a putative tum or suppressor gene may reside, deletional mapping was performed using 33 microsatellite markers spanning chromosome 1 in 30 patients with CM L BC (21 myeloid and 9 lymphoid). DNA was extracted from slides of bon e marrow smears or from bone marrow mononuclear cells. In each patient , DNA from chronic phase was analyzed alongside DNA from either their BC or accelerated phase. Allelic loss on Ip was observed in 14 of the 30 individuals (47%): 10 of the 21 myeloid and 4 of the 9 lymphoid BC cases. Serial cytogenetic information was available in 10 cases with L OH on Ip; interestingly, deletions in this region were not detected. T wo samples showed LOH at all informative loci on Ip, whereas the other 12 samples showed LOH on at least one but not all loci on Ip. The com mon region of LOH resided proximal to D1S508 and distal to D1S507(1p36 ). Our results suggest that a tumor suppressor gene that frequently pl ays an important role in the evolution to BC resides on 1p36 in CML. ( C) 1998 by The American society of Hematology.