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19202128
Patterns of microRNA expression characterize stages of human B-cell differentiation.

Blood, 2009/5/07;113(19):4586-94.

Zhang J[1], Jima DD, Jacobs C, Fischer R, Gottwein E, Huang G, Lugar PL, Lagoo AS, Rizzieri DA, Friedman DR, Weinberg JB, Lipsky PE, Dave SS

Affiliations

PMID: 19202128DOI: 10.1182/blood-2008-09-178186

Impact factor: 25.476

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.
MeSH terms
B-Lymphocytes; Blotting, Western; Burkitt Lymphoma; Cell Differentiation; Cell Lineage; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; MicroRNAs; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
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