Patterns of microRNA expression characterize stages of human B-cell differentiation.
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.
Zhang
Jenny
J
Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA
Jima
Dereje D
DD
Jacobs
Cassandra
C
Fischer
Randy
R
Gottwein
Eva
E
Huang
Grace
G
Lugar
Patricia L
PL
Lagoo
Anand S
AS
Rizzieri
David A
DA
Friedman
Daphne R
DR
Weinberg
J Brice
JB
Lipsky
Peter E
PE
Dave
Sandeep S
SS
D001402:B-Lymphocytes / Q000502:physiology*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs; D012333:RNA, Messenger