| First Author | Scaglione BJ | Year | 2007 |
| Journal | Br J Haematol | Volume | 139 |
| Issue | 5 | Pages | 645-57 |
| PubMed ID | 17941951 | Mgi Jnum | J:127719 |
| Mgi Id | MGI:3764742 | Doi | 10.1111/j.1365-2141.2007.06851.x |
| Citation | Scaglione BJ, et al. (2007) Murine models of chronic lymphocytic leukaemia: role of microRNA-16 in the New Zealand Black mouse model. Br J Haematol 139(5):645-57 |
| abstractText | Mouse models are valuable tools in the study of human chronic lymphocytic leukaemia (CLL). The New Zealand Black (NZB) strain is a naturally occurring model of late-onset CLL characterized by B-cell hyperproliferation and autoimmunity early in life, followed by progression to CLL. Other genetically engineered models of CLL that have been developed include (NZB x NZW) F1 mice engineered to express IL5, mice expressing human TCL1A, and mice overexpressing both BCL2 and a tumour necrosis factor receptor-associated factor. The applicability to human CLL varies with each model, suggesting that CLL is a multifactorial disease. Our work with the de novo NZB model has revealed many similarities to the human situation, particularly familial CLL. In NZB, the malignant clones express CD5, zap-70, and have chromosomal instability and germline Ig sequence. We also identified a point mutation in the 3'-flanking sequence of Mirn16-1, which resulted in decreased levels of the microRNA, miR-16 in lymphoid tissue. Exogenous restoration of miR-16 to an NZB malignant B-1 cell line resulted in cell cycle alterations, suggesting that the altered expression of Mirn15a/16-1 is an important molecular lesion in CLL. Future studies utilizing the NZB mouse could ascertain the role of environmental triggers, such as low dose radiation and organic chemicals in the augmentation of a pre-existing propensity to develop CLL. |
