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The discovery of a novel class of gene regulators, named microRNAs, has changed the landscape of human genetics. In hematopoiesis, recent work has improved our understanding of the role of microRNAs in hematopoietic differentiation and leukemogenesis.Using animal models engineered to overexpress miR-150, miR-17∼92 and miR-155 or to be deficient for miR-223, miR-155 and miR-17∼92 expression, several groups have now shown that miRNAs are critical for B-lymphocyte development (miR-150 and miR-17∼92), granulopoiesis (miR-223), immune function (miR-155) and B-lymphoproliferative disorders (miR-155 and miR-17∼92). Distinctive miRNA signatures have been described in association with cytogenetics and outcome in acute myeloid leukemia.There is now strong evidence that miRNAs modulate not only hematopoietic differentiation and proliferation but also activity of hematopoietic cells, in particular those related to immune function. Extensive miRNA deregulation has been observed in leukemias and lymphomas and mechanistic studies support a role for miRNAs in the pathogenesis of these disorders.