Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia

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Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia. / Reckzeh, Kristian; Cammenga, Jörg.

I: International Journal of Hematology, Vol. 91, Nr. 4, 2010, s. 557-568.

Forskningsoutput: TidskriftsbidragÖversiktsartikel

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Reckzeh, Kristian ; Cammenga, Jörg. / Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia. I: International Journal of Hematology. 2010 ; Vol. 91, Nr. 4. s. 557-568.

RIS

TY - JOUR

T1 - Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia

AU - Reckzeh, Kristian

AU - Cammenga, Jörg

PY - 2010

Y1 - 2010

N2 - The CEBPA gene encodes a transcription factor protein that is crucial for granulocytic differentiation, regulation of myeloid gene expression and growth arrest. Mutations in one or both alleles of CEBPA are observed in about 10% of patients with acute myeloid leukemia (AML). Moreover, other genetic events associated with AML have been identified to deregulate C/EBP alpha expression and function at various levels. Recently developed mouse models that accurately mimic the genetic C/EBP alpha alterations in human AML demonstrate C/EBP alpha's gatekeeper function in the control of self-renewal and lineage commitment of hematopoietic stem cells (HSCs). Moreover, these studies indicate that CEBPA mutations affect HSCs in early leukemia development by inducing proliferation and limiting their lineage potential. However, the exact relationship between 'pre-leukemic' HCSs and those cells that finally initiate leukemia (leukemia-initiating cells) with disturbed differentiation and aberrant proliferation remains elusive. More research is needed to identify and characterize these functionally distinct populations and the exact role of the different genetic alterations in the process of leukemia initiation and maintenance.

AB - The CEBPA gene encodes a transcription factor protein that is crucial for granulocytic differentiation, regulation of myeloid gene expression and growth arrest. Mutations in one or both alleles of CEBPA are observed in about 10% of patients with acute myeloid leukemia (AML). Moreover, other genetic events associated with AML have been identified to deregulate C/EBP alpha expression and function at various levels. Recently developed mouse models that accurately mimic the genetic C/EBP alpha alterations in human AML demonstrate C/EBP alpha's gatekeeper function in the control of self-renewal and lineage commitment of hematopoietic stem cells (HSCs). Moreover, these studies indicate that CEBPA mutations affect HSCs in early leukemia development by inducing proliferation and limiting their lineage potential. However, the exact relationship between 'pre-leukemic' HCSs and those cells that finally initiate leukemia (leukemia-initiating cells) with disturbed differentiation and aberrant proliferation remains elusive. More research is needed to identify and characterize these functionally distinct populations and the exact role of the different genetic alterations in the process of leukemia initiation and maintenance.

KW - differentiation

KW - Myeloid

KW - C/EBP alpha

KW - Transcription factor

KW - AML

KW - Leukemia

KW - Bi-allelic mutation

U2 - 10.1007/s12185-010-0573-1

DO - 10.1007/s12185-010-0573-1

M3 - Review article

VL - 91

SP - 557

EP - 568

JO - Nippon Ketsueki Gakkai zasshi : journal of Japan Haematological Society

T2 - Nippon Ketsueki Gakkai zasshi : journal of Japan Haematological Society

JF - Nippon Ketsueki Gakkai zasshi : journal of Japan Haematological Society

SN - 0925-5710

IS - 4

ER -