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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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IMMUNOBIOLOGY

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

Jenny Zhang1,*, Dereje D. Jima1,*, Cassandra Jacobs1, Randy Fischer2, Eva Gottwein3, Grace Huang1, Patricia L. Lugar2,4, Anand S. Lagoo5, David A. Rizzieri4, Daphne R. Friedman4, J. Brice Weinberg4, Peter E. Lipsky2, and Sandeep S. Dave1,4

1 Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC; 2 Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD; and Departments of 3 Molecular Genetics and Microbiology and Center for Virology, 4 Medicine, and 5 Pathology, Duke University Medical Center, Durham, NC

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.


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