Molecular mechanisms underlying deregulation of C/EBPα in acute myeloid leukemia

被引:29
|
作者
Reckzeh, Kristian [1 ]
Cammenga, Jorg [1 ,2 ]
机构
[1] Lund Univ, Lund Stem Cell Ctr, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden
[2] Lund Univ, Dept Hematol, S-22184 Lund, Sweden
关键词
AML; Leukemia; Transcription factor; C/EBP alpha; Myeloid differentiation; Bi-allelic mutation; ENHANCER-BINDING-PROTEIN; INTERNAL TANDEM DUPLICATION; GENE-EXPRESSION PROFILES; GERMLINE CEBPA MUTATIONS; GRANULOCYTIC DIFFERENTIATION; UP-REGULATION; TRANSLATIONAL CONTROL; TRANSCRIPTION FACTORS; PROGENITOR CELLS; SELF-RENEWAL;
D O I
10.1007/s12185-010-0573-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:557 / 568
页数:12
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