Patterns of microRNA expression characterize stages of human B-cell differentiation

Jenny Zhang, Dereje D. Jima, Cassandra Jacobs, Randy Fischer, Eva Gottwein, Grace Huang, Patricia L. Lugar, Anand S. Lagoo, David A. Rizzieri, Daphne R. Friedman, J. Brice Weinberg, Peter E. Lipsky, Sandeep S. Dave

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells.

Original languageEnglish (US)
Pages (from-to)4586-4594
Number of pages9
JournalBlood
Volume113
Issue number19
DOIs
StatePublished - Nov 17 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Zhang, J., Jima, D. D., Jacobs, C., Fischer, R., Gottwein, E., Huang, G., Lugar, P. L., Lagoo, A. S., Rizzieri, D. A., Friedman, D. R., Weinberg, J. B., Lipsky, P. E., & Dave, S. S. (2009). Patterns of microRNA expression characterize stages of human B-cell differentiation. Blood, 113(19), 4586-4594. https://doi.org/10.1182/blood-2008-09-178186