ALLELOTYPE ANALYSIS IN THE EVOLUTION OF CHRONIC MYELOCYTIC-LEUKEMIA

To elucidate the genetic events that may play important roles in the p rogression of chronic myelocytic leukemia [CML), we performed alleloty pe analysis in 90 patients with CML as the disease transformed to acce lerated phase or blast crisis (21 myeloid and 9 lymphoid cases). DNAs were extracted from slides of bone marrow smears or from freshly isola ted hone marrow mononuclear cells. The DNAs from the same individuals in both chronic phase and either blast crisis or accelerated phase wer e analyzed at 82 microsatellite markers, which mapped to each of the a utosomal arms except, the short arms of the acrocentric chromosomes. L oss of heterozygosity (LOH) on at least one locus was observed in 21 o f the 30 cases (70%) as the disease progressed, Frequent allelic loss of greater than or equal to 20% of the informative cases was observed on chromosome arms 1p (35%), 7p [21%), 19p (20%), and 20q (29%). Allel ic losses were also analyzed according to phenotypes. LOH of greater t han or equal to 20% was detected on 1p (29%), 18p (20%), and 20q (27%) in myeloid blast crisis, and on Ip (50%), 4p (25%), 7p (43%), 9p (29% ), 18q (25%), 19p (43%), and 20q (33%) in lymphoid blast crisis. Seria l cytogenetic information was available for most of our cases with LOH on these arms, and only one case had loss of both chromosomes 9 and 2 0. Fractional allelic loss, calculated for each sample as the total nu mber of chromosomal arms lost/total number of arms with information, s howed a median value of 0.06 and a mean of 0.098 (range 0 to 0.60)), T hese results suggest that tumor suppressor genes especially on Ip, 7p, 19p, and 20q probably have an important role in the progression to bl ast crisis of CML, (C) 1997 by The American Society oi Hematology.