Murine models of chronic lymphocytic leukaemia: role of microRNA-16 in the New Zealand Black mouse model.
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.
Scaglione
Brian J
BJ
New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Salerno
Erica
E
Balan
Murugabaskar
M
Coffman
Frederick
F
Landgraf
Pablo
P
Abbasi
Fatima
F
Kotenko
Sergei
S
Marti
Gerald E
GE
Raveche
Elizabeth S
ES
D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D051379:Mice; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D012334:RNA, Neoplasm / Q000235:genetics*
D035683:MicroRNAs; D012334:RNA, Neoplasm