Bone marrow cells from patients with acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS) who were previously treated with radiation and/or chemotherapy have a high frequency of clonal chromosome abnormalities. These abnormalities affect certain chromosomes preferentially: most patients have loss of either chromosome 5 or 7, deletion of part of the long arm of one of these chromosomes, or such abnormalities of both chromosomes 5 and 7. It has been shown that bands 5q23-q32 and 7q34-q35 are consistently missing in all patients whose cells contain a long arm deletion of one of these two chromosomes. We plan to assay leukemic cells from patients without karyotypically detectable deletions of these chromosomes to determine whether loss of heterozygosity for markers on them has occurred by other mechanisms, such as chromosome loss and duplication or mitotic recombination. If these mechanisms do occur, it can be argued that loss of activity of one or more suppressors of malignancy (""""""""anti-oncogenes"""""""") may be involved in the development of the leukemia. We have collected polymorphic probes from both chromosomes to be used in these assays. Since we have relatively few polymorphic probes from the regions that are commonly deleted, we will identify additional polymorphisms. In particular, chromosome walking and RNAse cleavage mapping will be used to find polymorphisms associated with growth factor genes that have been mapped to the critical region of chromosome 5. Results on 2 degrees ANLL will be compared those obtained on individuals with de novo ANLL. In some cases we will also be able to study the progression of the disease from MDS (""""""""preleukemia"""""""") to full-blown leukemia. The polymorphic probes will also be used to define as precisely as possible the chromosomal regions that are deleted in all patients who have deletions.
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