RT Journal Article
ID 21cb4ca922f1754b
A1 Paz-Priel , Ido
A1 Friedman, Alan
T1 C/EBPα Dysregulation in AML and ALL
JF Critical Reviews™ in Oncogenesis
JO CRO
YR 2011
FD 2011-12-05
VO 16
IS 1-2
SP 93
OP 102
K1 leukemia
K1 myeloid
K1 differentiation
K1 hematopoiesis
AB The transcription factor CCAAT/enhancer binding protein a (C/EBPα) is a critical regulator of myeloid development, directing granulocyte, and monocyte differentiation. As such, it is dysregulated in more than half of patients with acute myeloid leukemia (AML). C/EBPα expression is suppressed as result of common leukemia-associated genetic and epigenetic alterations such as AML1-ETO, BCR-ABL, FLT3-ITD, or CEBPA promoter methylation. In addition, 10-15% of patients with AML with intermediate risk cytogenetics are characterized by mutations of the CEBPA gene. Two classes of mutations are described. N-terminal changes result in expression of a truncated dominant negative C/EBPαp30 isoform. C-terminal mutations are in-frame insertions or deletions resulting in alteration of the leucine zipper preventing dimerization and DNA binding. Often, patients carry both N- and C-terminal mutations each affecting a different allele, and a mouse model recapitulates the human phenotype. Patients with mutated CEBPA AML comprise a clinically distinct group with favorable outcome consistently seen in patients with biallelic mutations. In addition, C/EBP family members are aberrantly expressing from the immunoglobulin heavy chain locus in 2% of pre-B ALLs. This review summarizes the normal hematopoietic developmental pathways regulated by C/EBPα and discusses the molecular pathways
involved in mutated CEBPA AML and ALL.
PB Begell House
LK https://www.dl.begellhouse.com/journals/439f422d0783386a,049e8a5e62fb019e,21cb4ca922f1754b.html