|
|
Blood, 16 April 2009, Vol. 113, No. 16, pp. 3754-3764.
Prepublished online as a Blood First Edition Paper on December 1, 2008; DOI 10.1182/blood-2008-10-184077.
 Previous Article | Next Article 
Submitted October 16, 2008
Accepted November 20, 2008
Differentiation-stage-specific expression of microRNAs in B-lymphocytes and diffuse large B-cell lymphomas
Raquel Malumbres, Kristopher A. Sarosiek, Elena Cubedo, Jose W Ruiz, Xiaoyu Jiang, Randy D Gascoyne, Robert Tibshirani, and Izidore S Lossos*
Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, United States
Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Department of Health Research and Policy, and Statistics, Stanford University, Stanford, CA, United States
* Corresponding author; email: ilossos{at}med.miami.edu.
miRNAs are small RNA molecules binding to partially complementary sites in the 3'-UTR of target transcripts and repressing their expression. miRNAs orchestrate multiple cellular functions and play critical roles in cell differentiation and cancer development. We analyzed miRNA profiles in B-cell subsets during peripheral B-cell differentiation as well as in diffuse large B-cell lymphoma (DLBCL) cells. Our results show temporal changes in the miRNA expression during B-cell differentiation with a highly unique miRNA profile in germinal center (GC) lymphocytes. We provide experimental evidence that these changes may be physiologically relevant by demonstrating that GC-enriched hsa-miR-125b down-regulates the expression of IRF4 and PRDM1/BLIMP1 and memory B-cell enriched hsa-miR-223 down-regulates the expression of LMO2. We further demonstrate that although an important component of the biology of a malignant cell is inherited from its non-transformed cellular progenitor - GC centroblasts - aberrant miRNA expression is acquired upon cell transformation. A 9 miRNAs signature was identified that could precisely differentiate the two major subtypes of DLBCL. Finally, expression of some of the miRNAs in this signature is correlated with clinical outcome of uniformly treated DLBCL patients.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. M. C. Ohlsson Teague, C. G. Print, and M. L. Hull
The role of microRNAs in endometriosis and associated reproductive conditions
Hum. Reprod. Update,
September 22, 2009;
(2009)
dmp034v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Tam
Micro-classifying diffuse large B-cell lymphomas
Blood,
June 25, 2009;
113(26):
6506 - 6507.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Li, S.-W. Kim, D. Rai, A. R. Bolla, S. Adhvaryu, M. C. Kinney, R. S. Robetorye, and R. C. T. Aguiar
Copy number abnormalities, MYC activity, and the genetic fingerprint of normal B cells mechanistically define the microRNA profile of diffuse large B-cell lymphoma
Blood,
June 25, 2009;
113(26):
6681 - 6690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
