Altered Expression of miR-16 Important Lesion in CLL Mice

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Br J Haematol. 2007 Oct 17; [Epub ahead of print]

Murine models of chronic lymphocytic leukaemia: role of microRNA-16

in the New Zealand Black mouse model.

Scaglione BJ, Salerno E, Balan M, Coffman F, Landgraf P, Abbasi F,

Kotenko S, Marti GE, Raveche ES.

New Jersey Medical School, University of Medicine and Dentistry of

New Jersey, Newark, NJ, USA.

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.

PMID: 17941951 [PubMed - as supplied by publisher]