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CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras andjunD

Nicolaou, Fotini, Teodoridis, Jens M., Park, Heiyoung, Georgakis, Alexander, Farokhzad, Omid C., Böttinger, Erwin P., Da Silva, Nicolas, Rousselot, Philippe, Chomienne, Christine, Ferenczi, Katalin, Arnaout, M. Amin, Shelley, C. Simon·2003·Blood
DOI 10.1182/blood-2002-01-0324
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Abstract

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 CD11c gene expression in HCL theCD11c gene promoter was characterized. Transfection of theCD11c promoter linked to a luciferase reporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11c promoter 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 reducedCD11c promoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11c promoter. 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 CD11c promoter 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 ras and junD.

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Metadata

Authors
Nicolaou, F., Teodoridis, J. M., Park, H., Georgakis, A., Farokhzad, O. C., Böttinger, E. P., Da Silva, N., Rousselot, P., Chomienne, C., Ferenczi, K., Arnaout, M. A., & Shelley, C. S.
Affiliations
From the Renal Unit, Massachusetts General Hospital, Charlestown, MA; the Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA; the Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY; Institut de Hematologié, Hôpital Saint-Louis, Paris, France; and the Department of Dermatology, Brigham and Women's Hospital, Boston, MA.
Venue
Blood
Publisher
American Society of Hematology
Published
2003-05-15
Volume
101
Issue
10
Pages
4033-4041
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood-2002-01-0324
Cited by
39
References
4
Language
en

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CoChat. (2026). Citation check: CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras andjunD. https://app.cochat.ai/papers/10.1182/blood-2002-01-0324
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Nicolaou, F., Teodoridis, J. M., Park, H., Georgakis, A., Farokhzad, O. C., Böttinger, E. P., Da Silva, N., Rousselot, P., Chomienne, C., Ferenczi, K., Arnaout, M. A., & Shelley, C. S. (2003). CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras andjunD. Blood. https://doi.org/10.1182/blood-2002-01-0324