This subproject proposes a molecular cytogenetic approach to study marrow transplantation. To date, analyses of the genetic origin of hematopoietic cells post-transplant have been done primarily using cytogenetic techniques and have thus been limited to analysis of sex mismatched donor-recipient pairs. Here techniques for determining genetic origin using DNA restriction fragment length polymorphisms (RFLP) will be developed. RFLP analyses will be used to determine the frequency and causes of the leukemic transformation of donor cells posttransplant. RFLP analysis will also be used in conjunction with cytogenetic analysis to study the frequency and duration of mixed hematopoietic and lymphoid chimerism posttransplant and its relation to clinical outcome (i.e. relapse, GVHD, rejection, graft failure, etc.). Genetic differences between patients with CML in chronic phase, accelerated phase and blast crisis will also be analyzed to determine whether specific chromosomal abnormalities predispose to posttransplant relapse. Correlation between karyotypic changes and the frequency and timing of posttransplant relapse will be assessed using both cytogenetic and molecular genetic techniques. In addition, we will attempt to clone gene(s) which may be related to the clinical progression of CML and determine whether its expression can be correlated with posttransplant relapse.
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