Induction of C/EBPα activity alters gene expression and differentiation of human CD34+ cells

Cammenga, Jörg; Mulloy, James C.; Berguido, Francisco J.; MacGrogan, Donal; Viale, Agnès; Nimer, Stephen D.

doi:10.1182/blood-2002-05-1546

Cited by 81 publications

(75 citation statements)

References 44 publications

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“…26 Contrarily, in CEBPA-mutated AML, the N-terminal mutation leading to formation of the truncated 30-kDa isoform originating from an internal ATG site acts as a dominant-negative inhibitor of CEBPA, inhibiting thereby the trans-activation of granulocyte target genes, leading to a blockage of granulocytic differentiation. Thus, we could reasonably hypothesize that wild-type CEBPA patients could display significantly different levels of S100A8 protein compared with patients with mutated CEBPA, thus arguing for the prognostic interest of an S100A8 assay for AML at the time of diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients

et al. 2010

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“…39,40 This would be in line with the observation that ectopic expression of C/EBPa in human CD34 positive cells induced granulocytic differentiation and inhibited erythrocytic differentiation, while strongly inducing ID1 expression in these cells. 41 Potentially, a similar mode of action might be operational at other differentiation pathway crossroads, for instance at the neutrophil-eosinophil branchpoint, as ectopic expression of ID1 inhibited the growth of CD34 positive cord blood cells that were stimulated with IL-5, which induces eosinophilic rather than neutrophilic differentiation (PJ Coffer et al, Blood 2003; 102(11): abstract 49).…”

Section: Discussionmentioning

confidence: 99%

ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells

Nigten

Ridder

Erpelinck-Verschueren

et al. 2005

Leukemia

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Acute promyelocytic leukemia (APL) is uniquely sensitive to treatment with all-trans retinoic acid (ATRA), which results in the expression of genes that induce the terminal granulocytic differentiation of the leukemic blasts. Here we report the identification of two ATRA responsive genes in APL cells, ID1 and ID2. These proteins act as antagonists of basic helix-loophelix (bHLH) transcription factors. ATRA induced a rapid increase in ID1 and ID2, both in the APL cell line NB4 as well as in primary patient cells. In addition, a strong downregulation of E2A was observed. E2A acts as a general heterodimerization partner for many bHLH proteins that are involved in differentiation control in various tissues. The simultaneous upregulation of ID1 and ID2, and the downregulation of E2A suggest a role for bHLH proteins in the induction of differentiation of APL cells following ATRA treatment. To test the relevance of this upregulation, ID1 and ID2 were overexpressed in NB4 cells. Overexpression inhibited proliferation and induced a G0/G1 accumulation. These results indicate that ID1 and ID2 are important retinoic acid responsive genes in APL, and suggest that the inhibition of specific bHLH transcription factor complexes may play a role in the therapeutic effect of ATRA in APL.

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“…CEBPA play a crucial role in granulocytic differentiation and could block the progression from the G1 to S phase thus by inducing the terminal differentiation of haematopoietic cells (Friedman et al, 2002;Cammenga et al, 2003). Deregulation of CEBPA activity is widely known to contribute to the myeloid transformation via reducing the differentiation potential (Wang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients

Sarojam

Raveendran²,

Vijay³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Induction of C/EBPα activity alters gene expression and differentiation of human CD34+ cells

Cited by 81 publications

References 44 publications

Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients

Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients

ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells

Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients

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