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Oncotarget 2016 Sep 20;7(38):60986-99

Role of Mir-15A/16-1 in Early B Cell Development in a Mouse Model of Chronic Lymphocytic Leukemia.

Underbayev C, Kasar S, Ruezinsky W, Degheidy H, Schneider JS, Marti G, Bauer SR, Fraidenraich D, Lightfoote MM, Parashar V, Raveche E, Batish M

Abstract

In both human chronic lymphocytic leukemia (CLL) and the New Zealand Black (NZB) murine model of CLL, decreased levels of microRNAs miR-15a/16 play an important role in the disease. Here we investigate the effects of this microRNA on early steps of B cell development and the capacity of miR-15a-deficient hematopoietic stem cells (HSC) and B1 progenitor cells (B1P) to reproduce CLL-like phenotype both in vitro and in vivo. Our results demonstrate that both miR-15a deficient HSC and B1P cells are capable of repopulating irradiated recipients and produce higher numbers of B1 cells than sources with normal miR-15a/16 levels. Furthermore, induced pluripotent stem (iPS) cells derived for the first time from NZB mice, provided insights into the B cell differentiation roadblock inherent in this strain. In addition, exogenously delivered miR-15a into the NZB derived B cell line provided valuable clues into novel targets such as Mmp10 and Mt2. Our data supports the hypothesis that miR-15a/16 deficient stem cells and B1Ps experience a maturation blockage, which contributes to B1 cells bias in development. This work will help understand the role of miR-15a in early events of CLL and points to B1P cells as potential cells of origin for this incurable disease.


Category: Journal Article
PubMed ID: #27533467 DOI: 10.18632/oncotarget.11290
Includes FDA Authors from Scientific Area(s): Biologics Medical Devices
Entry Created: 2016-02-19 Entry Last Modified: 2018-07-01
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