Patterns of micro RNA 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. 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 microRNAs, but rather maintain the microRNA-expression patterns of their normal B-cell counterparts. Further, each tumor-type maintained the expression of the lineage-specific microRNAs and expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in over 90% 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. Burkitt lymphoma, Chronic Lymphocytic Leukemia (Mutated), Chronic Lymphocytic Leukemia (Unmutated), Activated B cell-like Diffuse large B cell lymphoma, and Germinal Center-like Diffuse large B cell lymphoma Samples,