Deciphering the role of microRNA-708 in precursor B-cell acute lymphoblastic leukemia biology
dc.contributor.author | Doshi, Kshama Atul | |
dc.date.accessioned | 2012-09-21T16:45:16Z | |
dc.date.available | 2013-06-03T13:19:28Z | |
dc.date.issued | 2012 | |
dc.identifier.uri | http://hdl.handle.net/10713/2160 | |
dc.description | University of Maryland, Baltimore. Molecular Medicine. M.S. 2012 | en_US |
dc.description.abstract | MicroRNAs (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 biology | en_US |
dc.language.iso | en_US | en_US |
dc.subject | B-ALL | en_US |
dc.subject.mesh | Hematopoiesis | en_US |
dc.subject.mesh | MicroRNAs | en_US |
dc.subject.mesh | Precursor B-Cell Lymphoblastic Leukemia-Lymphoma | en_US |
dc.title | Deciphering the role of microRNA-708 in precursor B-cell acute lymphoblastic leukemia biology | en_US |
dc.contributor.advisor | Civin, Curt I. | |
dc.identifier.ispublished | No | en_US |
dc.description.uriname | Full Text | en_US |
refterms.dateFOA | 2019-02-21T01:58:22Z |