Regulation of the C/EBPα signaling pathway in acute myeloid leukemia (Review)
- Authors:
- Guanhua Song
- Lin Wang
- Kehong Bi
- Guosheng Jiang
-
Affiliations: Department of Hemato-Oncology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare and Uncommon Diseases, Key Medical Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology of Shandong Province, Jinan, Shandong 250062, P.R. China, Research Center for Medical Biotechnology, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China, Department of Hematology, Qianfoshan Mountain Hospital of Shandong University, Jinan, Shandong 250014, P.R. China - Published online on: March 10, 2015 https://doi.org/10.3892/or.2015.3848
- Pages: 2099-2106
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|
Roe JS and Vakoc CR: C/EBPα: Critical at the origin of leukemic transformation. J Exp Med. 211:1–4. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Rosenbauer F and Tenen DG: Transcription factors in myeloid development: Balancing differentiation with transformation. Nat Rev Immunol. 7:105–117. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Scott LM, Civin CI, Rorth P and Friedman AD: A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood. 80:1725–1735. 1992.PubMed/NCBI | |
|
Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon JI, Landschulz WH and McKnight SL: Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 3:1146–1156. 1989. View Article : Google Scholar : PubMed/NCBI | |
|
Koschmieder S, Halmos B, Levantini E and Tenen DG: Dysregulation of the C/EBPalpha differentiation pathway in human cancer. J Clin Oncol. 27:619–628. 2009. View Article : Google Scholar : | |
|
Mueller BU and Pabst T: C/EBPalpha and the pathophysiology of acute myeloid leukemia. Curr Opin Hematol. 13:7–14. 2006. View Article : Google Scholar | |
|
Zhang P, Iwasaki-Arai J, Iwasaki H, et al: Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha. Immunity. 21:853–863. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ and Tenen DG: Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci USA. 94:569–574. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Porse BT, Bryder D, Theilgaard-Mönch K, Hasemann MS, Anderson K, Damgaard I, Jacobsen SE and Nerlov C: Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage. J Exp Med. 202:85–96. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Scott E, Sawyers CL and Friedman AD: C/EBPalpha bypasses granulocyte colony-stimulating factor signals to rapidly induce PU.1 gene expression, stimulate granulocytic differentiation, and limit proliferation in 32D cl3 myeloblasts. Blood. 94:560–571. 1999.PubMed/NCBI | |
|
Bereshchenko O, Mancini E, Moore S, Bilbao D, Månsson R, Luc S, Grover A, Jacobsen SE, Bryder D and Nerlov C: Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML. Cancer Cell. 16:390–400. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W and Tenen DG: Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet. 27:263–270. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Preudhomme C, Sagot C, Boissel N, et al: ALFA Group: Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: A study from the Acute Leukemia French Association (ALFA). Blood. 100:2717–2723. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Miller M, Shuman JD, Sebastian T, Dauter Z and Johnson PF: Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha. J Biol Chem. 278:15178–15184. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Pabst T and Mueller BU: Transcriptional dysregulation during myeloid transformation in AML. Oncogene. 26:6829–6837. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Pabst T and Mueller BU: Complexity of CEBPA dysregulation in human acute myeloid leukemia. Clin Cancer Res. 15:5303–5307. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Cai DH, Wang D, Keefer J, Yeamans C, Hensley K and Friedman AD: C/EBP alpha:AP-1 leucine zipper heterodimers bind novel DNA elements, activate the PU.1 promoter and direct monocyte lineage commitment more potently than C/EBP alpha homodimers or AP-1. Oncogene. 27:2772–2779. 2008. View Article : Google Scholar | |
|
Wang D, Paz-Priel I and Friedman AD: NF-kappa B p50 regulates C/EBP alpha expression and inflammatory cytokine-induced neutrophil production. J Immunol. 182:5757–5762. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Dahl R, Walsh JC, Lancki D, Laslo P, Iyer SR, Singh H and Simon MC: Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPalpha ratio and granulocyte colony-stimulating factor. Nat Immunol. 4:1029–1036. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Licht JD, Chomienne C, Goy A, et al: Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17). Blood. 85:1083–1094. 1995.PubMed/NCBI | |
|
Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S and Zelent A: Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 12:1161–1167. 1993.PubMed/NCBI | |
|
Girard N, Tremblay M, Humbert M, Grondin B, Haman A, Labrecque J, Chen B, Chen Z, Chen SJ and Hoang T: RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells. Proc Natl Acad Sci USA. 110:13522–13527. 2013. View Article : Google Scholar | |
|
Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang DE and Tenen DG: AML1-ETO downregulates the granulocytic differentiation factor C/EBP alpha in t(8;21) myeloid leukemia. Nat Med. 7:444–451. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Baer C, Claus R, Frenzel LP, et al: Extensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia. Cancer Res. 72:3775–3785. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Chim CS, Wong AS and Kwong YL: Infrequent hypermethylation of CEBPA promotor in acute myeloid leukaemia. Br J Haematol. 119:988–990. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Annamaneni S, Kagita S, Gorre M, Digumarti RR, Satti V and Battini MR: Methylation status of CEBPA gene promoter in chronic myeloid leukemia. Hematology. 19:42–44. 2014. View Article : Google Scholar | |
|
Nikoloski G, Langemeijer SM, Kuiper RP, et al: Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet. 42:665–667. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Herrera-Merchan A, Arranz L, Ligos JM, de Molina A, Dominguez O and Gonzalez S: Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease. Nat Commun. 3:6232012. View Article : Google Scholar : PubMed/NCBI | |
|
Thiel AT, Feng Z, Pant DK, Chodosh LA and Hua X: The trithorax protein partner menin acts in tandem with EZH2 to suppress C/EBPα and differentiation in MLL-AF9 leukemia. Haematologica. 98:918–927. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Dedhia PH, Keeshan K, Uljon S, Xu L, Vega ME, Shestova O, Zaks-Zilberman M, Romany C, Blacklow SC and Pear WS: Differential ability of Tribbles family members to promote degradation of C/EBPalpha and induce acute myelogenous leukemia. Blood. 116:1321–1328. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshida A, Kato JY, Nakamae I and Yoneda-Kato N: COP1 targets C/EBPα for degradation and induces acute myeloid leukemia via Trib1. Blood. 122:1750–1760. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Pal P, Lochab S, Kanaujiya JK, Kapoor I, Sanyal S, Behre G and Trivedi AK: E6AP, an E3 ubiquitin ligase negatively regulates granulopoiesis by targeting transcription factor C/EBPα for ubiquitin-mediated proteasome degradation. Cell Death Dis. 4:e5902013. View Article : Google Scholar | |
|
Sandoval S, Kraus C, Cho EC, et al: Sox4 cooperates with CREB in myeloid transformation. Blood. 120:155–165. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Aue G, Du Y, Cleveland SM, et al: Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia. Blood. 118:4674–4681. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Fung TK, Leung AY and So CW: Sox4you: A new player in C/EBPα leukemia. Cancer Cell. 24:557–559. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang H, Alberich-Jorda M, Amabile G, et al: Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia. Cancer Cell. 24:575–588. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kindler T, Lipka DB and Fischer T: FLT3 as a therapeutic target in AML: Still challenging after all these years. Blood. 116:5089–5102. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Kelly LM, Liu Q, Kutok JL, Williams IR, Boulton CL and Gilliland DG: FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood. 99:310–318. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Federzoni EA, Valk PJ, Torbett BE, Haferlach T, Löwenberg B, Fey MF and Tschan MP: PU.1 is linking the glycolytic enzyme HK3 in neutrophil differentiation and survival of APL cells. Blood. 119:4963–4970. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Federzoni EA, Humbert M, Torbett BE, Behre G, Fey MF and Tschan MP: CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation. Sci Rep. 4:42612014. View Article : Google Scholar : PubMed/NCBI | |
|
Diakiw SM, Kok CH, To LB, Lewis ID, Brown AL and D’Andrea RJ: The granulocyte-associated transcription factor Krüppel-like factor 5 is silenced by hypermethylation in acute myeloid leukemia. Leuk Res. 36:110–116. 2012. View Article : Google Scholar | |
|
Chan KT, Creed SJ and Bear JE: Unraveling the enigma: Progress towards understanding the coronin family of actin regulators. Trends Cell Biol. 21:481–488. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Moriceau S, Kantari C, Mocek J, et al: Coronin-1 is associated with neutrophil survival and is cleaved during apoptosis: Potential implication in neutrophils from cystic fibrosis patients. J Immunol. 182:7254–7263. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Federzoni EA, Humbert M, Valk PJ, Behre G, Leibundgut EO, Torbett BE, Fey MF and Tschan MP: The actin-binding protein CORO1A is a novel PU.1 (SPI1)- and CEBPA-regulated gene with significantly lower expression in APL and CEBPA-mutated AML patients. Br J Haematol. 160:855–859. 2013. View Article : Google Scholar | |
|
Bao L, Kimzey A, Sauter G, Sowadski JM, Lu KP and Wang DG: Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am J Pathol. 164:1727–1737. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Wulf GM, Ryo A, Wulf GG, Lee SW, Niu T, Petkova V and Lu KP: Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J. 20:3459–3472. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Rinehart-Kim J, Johnston M, Birrer M and Bos T: Alterations in the gene expression profile of MCF-7 breast tumor cells in response to c-Jun. Int J Cancer. 88:180–190. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Pulikkan JA, Dengler V, Peer Zada AA, Kawasaki A, Geletu M, Pasalic Z, Bohlander SK, Ryo A, Tenen DG and Behre G: Elevated PIN1 expression by C/EBPalpha-p30 blocks C/EBPalpha-induced granulocytic differentiation through c-Jun in AML. Leukemia. 24:914–923. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Rishi L, Hannon M, Salomè M, et al: Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation. Blood. 123:2389–2400. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Humbert M, Halter V, Shan D, Laedrach J, Leibundgut EO, Baerlocher GM, Tobler A, Fey MF and Tschan MP: Deregulated expression of Kruppel-like factors in acute myeloid leukemia. Leuk Res. 35:909–913. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Britschgi A, Trinh E, Rizzi M, Jenal M, Ress A, Tobler A, Fey MF, Helin K and Tschan MP: DAPK2 is a novel E2F1/KLF6 target gene involved in their proapoptotic function. Oncogene. 27:5706–5716. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Britschgi A, Simon HU, Tobler A, Fey MF and Tschan MP: Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2. Br J Haematol. 149:55–64. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Rizzi M, Tschan MP, Britschgi C, et al: The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells. J Leukoc Biol. 81:1599–1608. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Fang J, Menon M, Zhang D, Torbett B, Oxburgh L, Tschan M, Houde E and Wojchowski DM: Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2. Blood. 112:886–890. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Humbert M, Federzoni EA, Britschgi A, et al: The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors PU.1 and C/EBPα during granulocytic differentiation but repressed by PML-RARα in APL. J Leukoc Biol. 95:83–93. 2014. View Article : Google Scholar : | |
|
Porse BT, Pedersen TA, Xu X, Lindberg B, Wewer UM, Friis-Hansen L and Nerlov C: E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo. Cell. 107:247–258. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Song G, Li Y, Zhang Z, et al: c-myc but not Hif-1α-dependent downregulation of VEGF influences the proliferation and differentiation of HL-60 cells induced by ATRA. Oncol Rep. 29:2378–2384. 2013.PubMed/NCBI | |
|
Eklund E: The role of Hox proteins in leukemogenesis: Insights into key regulatory events in hematopoiesis. Crit Rev Oncog. 16:65–76. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Kroon E, Krosl J, Thorsteinsdottir U, Baban S, Buchberg AM and Sauvageau G: Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b. EMBO J. 17:3714–3725. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Collins C, Wang J, Miao H, Bronstein J, Nawer H, Xu T, Figueroa M, Muntean AG and Hess JL: C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proc Natl Acad Sci USA. 111:9899–9904. 2014. View Article : Google Scholar | |
|
Nerlov C and Ziff EB: CCAAT/enhancer binding protein-alpha amino acid motifs with dual TBP and TFIIB binding ability co-operate to activate transcription in both yeast and mammalian cells. EMBO J. 14:4318–4328. 1995.PubMed/NCBI | |
|
Müller C, Calkhoven CF, Sha X and Leutz A: The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF complex for proliferation arrest. J Biol Chem. 279:7353–7358. 2004. View Article : Google Scholar | |
|
Chen PL, Riley DJ, Chen Y and Lee WH: Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs. Genes Dev. 10:2794–2804. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler WJ and Timchenko NA: C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4. Mol Cell. 8:817–828. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Shimokawa T, Nunomura S, Enomoto Y and Ra C: Amino acid residues in the beta3 strand and subsequent loop of the conserved ETS domain that mediate basic leucine zipper (bZIP) recruitment and potentially distinguish functional attributes of ETS proteins. Biochem J. 430:129–139. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Shimokawa T, Nunomura S, Fujisawa D and Ra C: Identification of the C/EBPα C-terminal tail residues involved in the protein interaction with GABP and their potency in myeloid differentiation of K562 cells. Biochim Biophys Acta. 1829:1207–1217. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Lin RJ, Nagy L, Inoue S, Shao W, Miller WH Jr and Evans RM: Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature. 391:811–814. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Zapotocky M, Mejstrikova E, Smetana K, Stary J, Trka J and Starkova J: Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically. Cancer Lett. 319:144–153. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Tallman MS, Gilliland DG and Rowe JM: Drug therapy for acute myeloid leukemia. Blood. 106:1154–1163. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Chen P, Aimiuwu J, Xie Z, Wei X, Liu S, Klisovic R, Marcucci G and Chan KK: Biochemical modulation of aracytidine (Ara-C) effects by GTI-2040, a ribonucleotide reductase inhibitor, in K562 human leukemia cells. AAPS J. 13:131–140. 2011. View Article : Google Scholar : | |
|
Uy GL, Rettig MP, Motabi IH, et al: A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. 119:3917–3924. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Bai H, Cao Z, Deng C, Zhou L and Wang C: miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis. J Cancer Res Clin Oncol. 138:595–602. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Hickey CJ, Schwind S, Radomska HS, et al: Lenalidomide-mediated enhanced translation of C/EBPα-p30 protein up-regulates expression of the antileukemic microRNA-181a in acute myeloid leukemia. Blood. 121:159–169. 2013. View Article : Google Scholar : | |
|
Ko YC, Fang WH, Lin TC, Hou HA, Chen CY, Tien HF and Lin LI: MicroRNA let-7a-3 gene methylation is associated with karyotyping, CEBPA promoter methylation, and survival in acute myeloid leukemia. Leuk Res. 38:625–631. 2014. View Article : Google Scholar : PubMed/NCBI |
