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dc.contributor.authorDoshi, Kshama Atul
dc.date.accessioned2012-09-21T16:45:16Z
dc.date.available2013-06-03T13:19:28Z
dc.date.issued2012
dc.identifier.urihttp://hdl.handle.net/10713/2160
dc.descriptionUniversity of Maryland, Baltimore. Molecular Medicine. M.S. 2012en_US
dc.description.abstractMicroRNAs (miRs) are known to play major roles in both normal hematopoietic differentiation, as well as hematopoietic malignancies. In this work, we report that miR-708; a little studied miR, is up-regulated in most B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples compared to hematopoietic stem-progenitor cells (HSPCs) and mature healthy B-cells. Our first hypothesis in this regard was that miR-708 has an oncogene-like function in B-ALL biology. To test this hypothesis, we performed loss/gain of function assays to examine effect of miR-708 modulation on B-ALL cell proliferation. While overexpression of miR-708 failed to alter cell proliferation rate, knock-down of this miR conferred a growth disadvantage on B-ALL cell proliferation. Our second hypothesis was that accumulation of non-functional immature B cells in B-ALL is due to deregulated expression of miR-708 during B cell development. To test this hypothesis, we overexpressed miR-708 in donor murine hematopoietic progenitor (Lin-) cells and monitored their hematopoietic differentiation in recipient mice following bone marrow transplantation. Post transplantation, we failed to observe any influence of miR-708 on hematopoietic differentiation of Lin- cells. In addition, we also observed a positive correlation that exists between expression pattern of miR-708 and its host gene OdZ4. Hence, we hypothesize that up-regulated miR-708 could be a passenger of up-regulated OdZ4 in B-ALL. To test this hypothesis, we are currently examining effects of OdZ4 knock-down on B-ALL cell proliferation. In future we also propose to examine if miR-708 cooperates with OdZ4 function in B-ALL. Future work also needs to address if miR-708 affects oncogenic processes, other than growth, that could be involved in B-ALL biologyen_US
dc.language.isoen_USen_US
dc.subjectB-ALLen_US
dc.subject.meshHematopoiesisen_US
dc.subject.meshMicroRNAsen_US
dc.subject.meshPrecursor B-Cell Lymphoblastic Leukemia-Lymphomaen_US
dc.titleDeciphering the role of microRNA-708 in precursor B-cell acute lymphoblastic leukemia biologyen_US
dc.contributor.advisorCivin, Curt I.
dc.identifier.ispublishedNoen_US
dc.description.urinameFull Texten_US
refterms.dateFOA2019-02-21T01:58:22Z


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