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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4586-4594.
Prepublished online as a Blood First Edition Paper on February 6, 2009; DOI 10.1182/blood-2008-09-178186.
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Submitted September 9, 2008
Accepted January 27, 2009
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, and Sandeep S. Dave*
Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC, United States
Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, United States
Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, NC, United States
Department of Medicine, Duke University Medical Center, Durham, NC, United States
Department of Pathology, Duke University Medical Center, Durham, NC, United States
* Corresponding author; email: sandeep.dave{at}duke.edu.
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. Further, 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 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. While these tumors could be distinguished from each other using 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 over 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.
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