C/EBPalpha and the pathophysiology of acute myeloid leukemia

Mueller, Beatrice U; Pabst, Thomas (2006). C/EBPalpha and the pathophysiology of acute myeloid leukemia. Current opinion in hematology, 13(1), pp. 7-14. Hagerstown, Md.: Wolters Kluwer Lippincott Williams & Wilkins 10.1097/01.moh.0000190110.08156.96

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PURPOSE OF REVIEW: The transcription factor C/EBPalpha controls differentiation and proliferation in normal granulopoiesis in a stage-specific manner. Loss of C/EBPalpha function in myeloid cells in vitro and in vivo leads to a block to myeloid differentiation similar to that which is observed in malignant cells from patients with acute myeloid leukemia. The finding of C/EBPalpha alterations in subgroups of acute myeloid leukemia patients suggests a direct link between critically decreased C/EBPalpha function and the development of the disorder. RECENT FINDINGS: Conditional mouse models provide direct evidence that loss of C/EBPalpha function leads to the accumulation of myeloid blasts in the bone marrow. Targeted disruption of the wild type C/EBPalpha protein, while conserving the dominant-negative 30 kDa isoform of C/EBPalpha, induces an AML-like disease in mice. In hematopoietic stem cells C/EBPalpha serves to limit cell self-renewal. Finally, C/EBPalpha function is disrupted at different levels in specific subgroups of acute myeloid leukemia patients. SUMMARY: There is evidence that impaired C/EBPalpha function contributes directly to the development of acute myeloid leukemia. Normal myeloid development and acute myeloid leukemia are now thought to reflect opposite sides of the same hematopoietic coin. Restoring C/EBPalpha function represents a promising target for novel therapeutic strategies in acute myeloid leukemia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology > Centre of Competence for Psychosomatic Medicine
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Müller, Beatrice Ursula and Pabst, Thomas

ISSN:

1065-6251

ISBN:

16319681

Publisher:

Wolters Kluwer Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:46

Last Modified:

06 Dec 2013 13:41

Publisher DOI:

10.1097/01.moh.0000190110.08156.96

PubMed ID:

16319681

Web of Science ID:

000234078800002

URI:

https://boris.unibe.ch/id/eprint/18996 (FactScience: 1357)

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