Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas

Raquel Malumbres, Kristopher A. Sarosiek, Elena Cubedo, Jose Ruiz, Xiaoyu Jiang, Randy D. Gascoyne, Robert Tibshirani, Izidore Lossos

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

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 nontransformed cellular progenitor - GC centroblasts - aberrant miRNA expression is acquired upon cell transformation. A 9-miRNA signature was identified that could precisely differentiate the 2 major subtypes of DLBCL. Finally, expression of some of the miRNAs in this signature is correlated with clinical outcome of uniformly treated DLBCL patients.

Original languageEnglish
Pages (from-to)3754-3764
Number of pages11
JournalBlood
Volume113
Issue number16
DOIs
StatePublished - Nov 17 2009

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Lymphocytes
Lymphoma, Large B-Cell, Diffuse
MicroRNAs
B-Lymphocytes
Cells
Germinal Center
Cell Differentiation
Down-Regulation
B-Lymphocyte Subsets
3' Untranslated Regions
RNA
Data storage equipment
Molecules

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas. / Malumbres, Raquel; Sarosiek, Kristopher A.; Cubedo, Elena; Ruiz, Jose; Jiang, Xiaoyu; Gascoyne, Randy D.; Tibshirani, Robert; Lossos, Izidore.

In: Blood, Vol. 113, No. 16, 17.11.2009, p. 3754-3764.

Research output: Contribution to journalArticle

Malumbres, Raquel ; Sarosiek, Kristopher A. ; Cubedo, Elena ; Ruiz, Jose ; Jiang, Xiaoyu ; Gascoyne, Randy D. ; Tibshirani, Robert ; Lossos, Izidore. / Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas. In: Blood. 2009 ; Vol. 113, No. 16. pp. 3754-3764.
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AU - Gascoyne, Randy D.

AU - Tibshirani, Robert

AU - Lossos, Izidore

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