MOLECULAR CYTOGENETIC DELINEATION OF DELETIONS AND TRANSLOCATIONS INVOLVING CHROMOSOME BAND 7Q22 IN MYELOID LEUKEMIAS

Loss of chromosome 7 (-7) or deletion of its long arm (7q-) are recurr ing chromosome abnormalities in myeloid disorders, especially in thera py-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML). The association of -7/7q- with myeloid leukemia suggests tha t these regions contain a novel tumor suppressor gene(s) whose loss of function contributes to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified: one in band 7q22 and a second in bands 7q32-q35. We analyz ed bone marrow and blood samples from 21 patients with myeloid leukemi a (chronic myeloid leukemia, n=2; de novo MDS, n=4; de novo AML, n=13; t-AML, n=2) that on chromosome banding analysis exhibited deletions ( n=19) or reciprocal translocations (n=2) of band 7q22 using fluorescen ce in situ hybridization. As probes, we used Alu-polymerase chain reac tion products from 22 yeast artificial chromosome (YAC) clones that sp an chromosome bands 7q21.1-q32, including representative clones from a panel of YACs recognizing a contiguous genomic DNA fragment of 5 to 6 Mb in band 7q22. In the 19 cases with deletions, we identified two di stinct commonly deleted regions: one region within band 7q22 was defin ed by the two CML cases; the second region encompassed a distal part o f band 7q22 and the entire band 7q31 and was defined by the MDS/AML ca ses, The breakpoint of one of the reciprocal translocations was mapped to 7q21.3, which is centromeric to both of the commonly deleted regio ns, The breakpoint of the second translocation, which was present in u nstimulated bone marrow and phytohemagglutinin-stimulated blood of an MDS patient, was localized to a 400-kb genomic segment in 7q22 within the deletion cluster of the MDS/AML cases, In conclusion, our data sho w marked heterogeneity of 7q22 deletion and translocation breakpoints in myeloid leukemias, suggesting the existence of more than one pathog enetically relevant gene. (C) 1997 by The American Society of Hematolo gy.