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Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the β2 integrin CD11c. In order to determine the cause of CD11cgene expression in HCL theCD11cgene promoter was characterized. Transfection of theCD11cpromoter linked to a luciferasereporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11cpromoter is its interaction with the activator protein-1 (AP-1) family of transcription factors. Comparison of nuclear extracts prepared from hairy cells with those prepared from other cell types indicated that hairy cells exhibit abnormal constitutive expression of an AP-1 complex containing JunD. Functional inhibition of AP-1 expressed by hairy cells reducedCD11cpromoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11cpromoter. Furthermore, in the hairy cell line EH, inhibition of Ras signaling through mitogen-activated protein kinase/extracellular signal–regulated kinase kinases 1 and 2 (MEK1/2) reduced not only CD11cpromoter activity but also reduced both CD11c surface expression and proliferation. Expression in nonhairy cells of a dominant-positive Ras mutant activated the CD11cpromoter to levels equivalent to those in hairy cells. Together, these data indicate that the abnormal expression of the CD11cgene characteristic of HCL is dependent upon activation of the proto-oncogenes rasand junD.

CD43 is an abundant, heavily glycosylated molecule expressed specifically on the surface of leukocytes and platelets. When leukocytes are at rest, CD43 acts to prevent both homotypic and heterotypic interactions. However, during leukocyte activation CD43 expression is repressed, facilitating the intercellular contact required for chemotaxis, phagocytosis, aggregation, adhesion to endothelium, and transendothelial migration. Consequently, CD43 repression plays a vital role both in innate and acquired immunity. Here we report that a dramatic down-regulation of CD43 mRNA levels occurs during activation of the leukocytic cell line K562. This repression coincides with repression of the transcriptional activity of the CD43gene promoter. We have determined that heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and Purα act together to mediate repression of the CD43promoter during K562 activation. The hnRNP-K molecule and Purα bind single-stranded DNA. Therefore, exposure of single-stranded structures within theCD43promoter probably plays a major role in effectingCD43repression.