|
|
Blood, 15 June 2007, Vol. 109, No. 12, pp. 5079-5086.
Prepublished online as a Blood First Edition Paper on March 9, 2007; DOI 10.1182/blood-2007-02-071225.
 Previous Article | Next Article 
Submitted February 1, 2007
Accepted March 7, 2007
Abnormal microRNA-16 locus with synteny to human 13q14
linked to CLL in NZB mice
Elizabeth S Raveche, Erica Salerno, Brian J Scaglione, Vijaya Manohar, Fatima Abbasi, Yi-Chu Lin, Torgny Fredrickson, Pablo Landgraf, Sumant Ramachandra, Konrad Huppi, Jorge R Toro, Vincent E Zenger, Robert A Metcalf, and Gerald E Marti*
Department of Pathology & Laboratory Medicine, NJMS/UMDNJ, Newark, NJ, United States
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, United States
CBER, FDA/NIH, Bethesda, MD, United States
Lab of Immunopathology, NIAID/NIH, Bethesda, MD, United States
Lab of RNA Mol. Biol., Howard Hughes Med Inst, The Rockefeller University, New York, NY, United States
Global Development, Schering-Plough Res Inst, Kenilworth, NJ, United States
Gene Silencing Section, ATS/NCI/NIH, Gaithersburg, MD, United States
Genetic Epidemology Branch, DCEG/NCIPS, Rockville, MD, United States
* Corresponding author; email: gemarti{at}helix.nih.gov.
NZB mice, with autoimmune and B lymphoproliferative disease (B-LPD), are a model for human chronic lymphocytic leukemia (CLL). A genome-wide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content and microsatellite polymorphisms, 74 had disease. The CD5+, IgM+, B220 dim, hyperdiploid LPD was linked to three loci on chromosomes 14, 18 and 19 which are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs, mir15a/16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3'flanking sequence of the identical micro RNA, mir16-1 and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cell cycle alterations and increased apoptosis. Linkage of the mir15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the miR15a/16-1 is the molecular lesion in CLL.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
MicroRNAs play a role in neoplasia
- Thomas J. Kipps
Blood 2007 109: 5071-5072.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
G. A. Calin, A. Cimmino, M. Fabbri, M. Ferracin, S. E. Wojcik, M. Shimizu, C. Taccioli, N. Zanesi, R. Garzon, R. I. Aqeilan, et al.
MiR-15a and miR-16-1 cluster functions in human leukemia
PNAS,
April 1, 2008;
105(13):
5166 - 5171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Kipps
Chronic Lymphocytic Leukemia: Prognostic Markers and Revised Criteria for Treatment and Response Assessment
ASCO Educational Book,
January 1, 2008;
2008(1):
286 - 290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhang, J. E. Dahlberg, and W. Tam
MicroRNAs in Tumorigenesis: A Primer
Am. J. Pathol.,
September 1, 2007;
171(3):
728 - 738.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
