DETECTION OF SOMATIC GENE MUTATIONS IN HEMATOLOGIC DISEASES

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A number of hematologic diseases have been shown to result from clonal expansion of an abnormal stem cell. In a few cases, typically associated with macroscopic chromosomal structural abnormalities, individual genes have been implicated. Examples include chronic myelogenous leukemia (CML) and the BCR-Abl fusion gene, and acute promyelocytic leukemia (APL) and the retinoic acid receptor. Detection of a specific genetic abnormality has had a significant impact on the diagnosis and treatment of CML and APL. No specific or consistent genetic abnormality has been detected in the majority of clonal bone marrow disorders, including the myelodysplastic syndromes and the myeloproliferative syndromes other than CML. We are in the process of implementing representational difference analysis to look for changes in the somatic DNA of individuals with clonal bone marrow disorders. We have had promising results with our test samples. If these results are confirmed, we will proceed with the analysis of previously collected patient samples, using DNA collected from autologous cultured skin fibroblasts as a source of normal DNA and DNA collected from peripheral blood as a source of abnormal DNA.