| First Author | Underbayev C | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 38 | Pages | 60986-60999 |
| PubMed ID | 27533467 | Mgi Jnum | J:268963 |
| Mgi Id | MGI:6273546 | Doi | 10.18632/oncotarget.11290 |
| Citation | Underbayev C, et al. (2016) Role of mir-15a/16-1 in early B cell development in a mouse model of chronic lymphocytic leukemia. Oncotarget 7(38):60986-60999 |
| abstractText | 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. |
