Assessing Clonal Evolution and Specific Genetic Alterations in Myeloproliferative Neoplasms

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Abstract Summary

Myeloproliferative neoplasms (MPNs) are a group of bone marrow derived leukemia’s defined by overproduction of one or more myeloid blood cell lineages. MPNs contain genetic alterations which “clonally emerge” or arise as the disease progresses, resulting in a mixed pool of different clones. This makes identification of mutational hierarchy and analysis of individual alterations difficult. For this project we were able to successfully isolate, genotype, and retain material for downstream genetic and epigenetic analysis on specific clones within a single MPN patient using a human colony forming assay technique (CFA). In addition, we knocked down a novel, recurrently altered gene in MPNs, known as ethanolamine kinase (ETNK1) in zebrafish, an animal model that has conserved blood development with humans. We used a morpholino to successfully interrupt the ETNK1 gene found in out animal model. Our prelimary results suggest that loss of function of this gene may interuppt normal blood development, and may play a role in the pathogenesis of MPN's in humans.

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Spelman College
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