The goal of this project is to describe the properties of malignant and normal stem cells in relation to autologous marrow transplantation by studying the clonal characteristics of defined cell populations using X- linked or tumor-specific markers. this study will identify and follow cases of clonal hematopoiesis while in CR after therapy for acute leukemia which will determine prevalence and better describe the biologic nature of the leukemic stem cell. A determination of outcome in those individuals who proceed to AMT may ultimately improve results of therapy. Studies of N-ras and c-fms mutations will be the initial studies in identifying a marker, for this potentially early phase in the pathogenesis of leukemia. This study will determine the clonal origins of the malignant myeloma clone, utilizing the unique rearrangement sequence of the immunoglobulin heavy chain to analyze cell compartments representative of a differentiation stage defined by the presence or absence of certain cell surface antigens. Finally this study would demonstrate convincingly that clonal reconstitution of hematopoiesis after AMT does occur in humans. Using X-linked markers, serial samples would be analyzed from before and after transplant to detect shifting clonal ratios, indicating a change in contribution from the stem cell pool which would result, statistically, from a decreased stem cell population. The results of this analysis would be correlated with clinical outcome and associations to various kinds of ex vivo marrow manipulation would be sought.
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