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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, J; Jima, DD; Jacobs, C; Fischer, R; Gottwein, E; Huang, G; Lugar, PL; Lagoo, AS; Rizzieri, DA; Friedman, DR; Weinberg, JB; Lipsky, PE; Dave, SS

Published Date

  • May 7, 2009

Published In

Volume / Issue

  • 113 / 19

Start / End Page

  • 4586 - 4594

PubMed ID

  • 19202128

Pubmed Central ID

  • 19202128

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2008-09-178186

Language

  • eng

Conference Location

  • United States