Genomes and Genes
Gene Symbol: C/EBP
Description: CCAAT enhancer binding protein epsilon
Alias: C/EBP-epsilon, CRP1, CCAAT/enhancer-binding protein epsilon, CCAAT/enhancer binding protein (C/EBP), epsilon, c/EBP epsilon
- Shyamsunder P, Shanmugasundaram M, Mayakonda A, Dakle P, Teoh W, Han L, et al. Identification of a novel enhancer of CEBPE essential for granulocytic differentiation. Blood. 2019;: pubmed publisher..In summary, we have identified a novel enhancer crucial for regulating expression of Cebpe, and required for normal granulocytic differentiation. ..
- Glass C, Wuertzer C, Cui X, Bi Y, Davuluri R, Xiao Y, et al. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia. PLoS ONE. 2013;8:e67134 pubmed publisher..These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia. ..
- Li J, Dai Y, Lilljebjörn H, Shen S, Cui B, Bai L, et al. Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases. Proc Natl Acad Sci U S A. 2018;115:E11711-E11720 pubmed publisher..The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL. ..
- Ferrari R, Tadini L, Moratti F, Lehniger M, Costa A, Rossi F, et al. CRP1 Protein: (dis)similarities between Arabidopsis thaliana and Zea mays. Front Plant Sci. 2017;8:163 pubmed publisher..of chloroplast biogenesis by At5g42310, a member of the Arabidopsis PPR family which we here refer to as AtCRP1 (Chloroplast RNA Processing 1), providing a comparison with the orthologous ZmCRP1 protein from Zea maysMarchwicka A, Marcinkowska E. Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines. Int J Mol Sci. 2018;19: pubmed publisher..Our results suggest that CEBPB is the major VDR and RARA-responsive gene among the CEBP family, necessary for expression of genes connected with myeloid functions. ..Fujishiro T, Mashiko T, Masuoka Y, Yamada M, Furukawa D, Yazawa N, et al. Conversion surgery for an initially unresectable, locally advanced pancreatic cancer after induction chemotherapy and carbon-ion radiotherapy: a case report. Surg Case Rep. 2018;4:112 pubmed publisher..facility and was subsequently diagnosed with pancreatic cancer cStage III (Ph, TS2 (35 mm), cT4, cCH1, cDU1, cS1, cRP1, cPL1, cVsm0, cAsm1, cN0, cM0) that was also categorized as an unresectable LAPC...Larracas C, Hekman R, Dyrness S, Arata A, Williams C, Crawford T, et al. Comprehensive Proteomic Analysis of Spider Dragline Silk from Black Widows: A Recipe to Build Synthetic Silk Fibers. Int J Mol Sci. 2016;17: pubmed publisher..dope, and dragline silk contain at least seven common proteins: three members of the Cysteine-Rich Protein Family (CRP1, CRP2 and CRP4), cysteine-rich secretory protein 3 (CRISP3), fasciclin and two uncharacterized proteins...Okuma T, Hirata M, Yano F, Mori D, Kawaguchi H, Chung U, et al. Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding proteins. Biomed Res. 2015;36:21-9 pubmed publisher..C/EBPs may play a variety of roles in the homeostasis of joint cartilage under physiological and pathological conditions. ..Lieber S, Scheer F, Finkernagel F, Meissner W, Giehl G, Brendel C, et al. The inverse agonist DG172 triggers a PPARÎ²/Î´-independent myeloid lineage shift and promotes GM-CSF/IL-4-induced dendritic cell differentiation. Mol Pharmacol. 2015;87:162-73 pubmed publisher..Based on these data we developed a new compound, (Z)-2-(4-chlorophenyl)-3-[4-(4-methylpiperazine-1-yl)phenyl]acrylonitrile (DG228), which enhances DC differentiation in the absence of significant PPARÎ²/Î´ binding. ..Shyamsunder P, Sankar H, Mayakonda A, Han L, Nordin H, Woon T, et al. CARD10, a CEBPE target involved in granulocytic differentiation. Haematologica. 2018;103:1269-1277 pubmed publisher..Taken together, our data demonstrate for the first time that Card10 is expressed in granulocytes and is a direct target of CEBPE with functions extending to myeloid differentiation. ..Aung H, Dixon L, Smith L, Sweeney N, Robson J, Berney M, et al. Novel regulatory roles of cAMP receptor proteins in fast-growing environmental mycobacteria. Microbiology. 2015;161:648-61 pubmed publisher..saprophytic, mycobacterial species that contains two cAMP-receptor protein (CRP) homologues designated herein as Crp1 and Crp2...Pombo de Oliveira M, Emerenciano M, Winn A, Costa I, Mansur M, Ford A. Concordant B-cell precursor acute lymphoblastic leukemia in non-twinned siblings. Blood Cells Mol Dis. 2015;54:110-5 pubmed publisher..Altogether, our data suggest that genetic predisposition aligned with chance haa an additive effect in BCP-ALL outcome. ..Jones H, Yoo J, Crother T, Kyme P, Ben Shlomo A, Khalafi R, et al. Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury independent of neutrophil infiltration. PLoS ONE. 2015;10:e0123460 pubmed publisher..These findings suggest that pulmonary neutrophilia is not linked to hypoxemia in ventilator-induced lung injury, and that nicotinamide exacerbates hypoxemia during VILI. ..Zheng S, Chang W, Li C, Lou H. Als1 and Als3 regulate the intracellular uptake of copper ions when Candida albicans biofilms are exposed to metallic copper surfaces. FEMS Yeast Res. 2016;16: pubmed publisher..Transcriptional analysis revealed that the expression of copper transporter-related gene, CRP1, was significantly increased in als1/als1, als3/als3, suggesting a potential role of ALS1 and ALS3 in absorbing ..Urayama K, Takagi M, Kawaguchi T, Matsuo K, Tanaka Y, Ayukawa Y, et al. Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese. Sci Rep. 2018;8:789 pubmed publisher..This study represents a first step towards characterizing the role of genetic susceptibility in childhood ALL risk in Japanese. ..Eriguchi Y, Nakamura K, Hashimoto D, Shimoda S, Shimono N, Akashi K, et al. Decreased secretion of Paneth cell Î±-defensins in graft-versus-host disease. Transpl Infect Dis. 2015;17:702-6 pubmed publisher..We directly measured Î±-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay...Lee Y, Jones L, Timchenko N, Perrotti D, Tenen D, Kogan S. CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities. Blood. 2006;108:2416-9 pubmed..We also show that forced expression of C/EBPalpha or C/EBPepsilon in combination with ATRA treatment has a synergistic effect on survival of leukemic mice compared with either therapy alone. ..Wang Y, Chen J, Li J, Deng J, Rui Y, Lu Q, et al. Association of three polymorphisms in ARID5B, IKZF1 and CEBPE with the risk of childhood acute lymphoblastic leukemia in a Chinese population. Gene. 2013;524:203-7 pubmed publisher..Statistically significant differences were not found in the SNPs for IKZF1 and CEBPE. In conclusion, ARID5B rs10821936 could serve as a potential biomarker for assessing the risk of childhood ALL in Chinese children. ..Gharbi H, Ben Hassine I, Soltani I, Safra I, Ouerhani S, Bel Haj Othmen H, et al. Association of genetic variation in IKZF1, ARID5B, CDKN2A, and CEBPE with the risk of acute lymphoblastic leukemia in Tunisian children and their contribution to racial differences in leukemia incidence. Pediatr Hematol Oncol. 2016;33:157-67 pubmed publisher..These differences, combined with differences in linkage disequilibrium structure between populations and differences in size between populations, may contribute to racial differences in pediatric ALL incidence. ..Zaidi M, O Leary S, Wu S, Chabot D, Gleddie S, Laroche A, et al. Investigating Triticeae anther gene promoter activity in transgenic Brachypodium distachyon. Planta. 2017;245:385-396 pubmed publisher..as well as the tapetum-specific genes chalcone synthase-like 1 (CHSL1), from wheat and cysteine-rich protein 1 (CRP1) from triticale were fused to the green fluorescent protein gene (GFP) and analyzed in transgenic Brachypodium...Bekker Mendez V, Núñez Enríquez J, Torres Escalante J, Alvarez Olmos E, González Montalvoc P, Jimenez Hernandez E, et al. ARID5B, CEBPE and PIP4K2A Germline Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia in Mexican Patients: A MIGICCL Study. Arch Med Res. 2016;47:623-628 pubmed publisher..1, CI 95% (2.0-4.8), respectively). Otherwise, the rs7088318 (PIP4K2A) and rs2239633 (CEBPE) polymorphisms were not associated with ALL risk. Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population. ..Xu X, Ren X, Wang H, Zhao Y, Yi Z, Wang K, et al. Identification and functional analysis of acute myeloid leukemia susceptibility associated single nucleotide polymorphisms at non-protein coding regions of RUNX1. Leuk Lymphoma. 2016;57:1442-9 pubmed publisher..Supershift assay indicated that one potential binding protein was PU.1. To sum up, rs2268276 and especially rs2249650 may be qualified as new acute myeloid leukemia susceptibility-associated SNPs. ..Studd J, Yang M, Li Z, Vijayakrishnan J, Lu Y, Yeoh A, et al. Genetic predisposition to B-cell acute lymphoblastic leukemia at 14q11.2 is mediated by a CEBPE promoter polymorphism. Leukemia. 2019;33:1-14 pubmed publisher..Finally, we map IGH-CEBPE translocation breakpoints in two cases, implicating RAG recombinase activity in their formation. ..Tian Y, Wang G, Hu Q, Xiao X, Chen S. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer. J Cell Biochem. 2017;: pubmed publisher..Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. This article is protected by copyright. All rights reserved...Malu K, Garhwal R, Pelletier M, Gotur D, Halene S, Zwerger M, et al. Cooperative Activity of GABP with PU.1 or C/EBP? Regulates Lamin B Receptor Gene Expression, Implicating Their Roles in Granulocyte Nuclear Maturation. J Immunol. 2016;197:910-22 pubmed publisher..These findings demonstrate that GABP, PU.1, and C/EBP? cooperate to control transcription of the gene encoding LBR, a nuclear envelope protein that is required for the characteristic lobulated morphology of mature neutrophils. ..Hsu L, Briggs F, Shao X, Metayer C, Wiemels J, Chokkalingam A, et al. Pathway Analysis of Genome-wide Association Study in Childhood Leukemia among Hispanics. Cancer Epidemiol Biomarkers Prev. 2016;25:815-22 pubmed publisher..Cancer Epidemiol Biomarkers Prev; 25(5); 815-22. Â©2016 AACR. ..Lopez A, Wang C, Huang C, Yaman I, Li Y, Chakravarty K, et al. A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation. Biochem J. 2007;402:163-73 pubmed..These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism. ..Xu H, Yang W, Pérez Andreu V, Devidas M, Fan Y, Cheng C, et al. Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations. J Natl Cancer Inst. 2013;105:733-42 pubmed publisher..These findings indicate strong associations between inherited genetic variation and ALL susceptibility in children and shed new light on ALL molecular etiology in diverse ancestry. ..Gery S, Park D, Vuong P, Chih D, Lemp N, Koeffler H. Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes. Blood. 2004;104:3911-7 pubmed..RA signaling in granulocytic differentiation involves regulated expression of CHOP and C/EBPepsilon in a coordinated fashion. ..Chih D, Park D, Gross M, Idos G, Vuong P, Hirama T, et al. Protein partners of C/EBPepsilon. Exp Hematol. 2004;32:1173-81 pubmed..Our results suggest heterodimeric partners of C/EBPepsilon modulate the function of C/EBPepsilon in mediating gene transcription during myelopoiesis. ..Larsen M, Häger M, Glenthøj A, Asmar F, Clemmensen S, Mora Jensen H, et al. miRNA-130a regulates C/EBP-? expression during granulopoiesis. Blood. 2014;123:1079-89 pubmed publisher..We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-? during granulopoiesis. ..Bhandari P, Ahmad F, Mandava S, Das B. Association of Genetic Variants in ARID5B, IKZF1 and CEBPE with Risk of Childhood de novo B-Lineage Acute Lymphoblastic Leukemia in India. Asian Pac J Cancer Prev. 2016;17:3989-95 pubmed..Understanding the effects of these variants in different ethnic groups is crucial as they may confer different risk of ALL within different populations. ..Bartram T, Burkhardt B, Wössmann W, Seidemann K, Zimmermann M, Cario G, et al. Childhood acute lymphoblastic leukemia-associated risk-loci IKZF1, ARID5B and CEBPE and risk of pediatric non-Hodgkin lymphoma: a report from the Berlin-Frankfurt-Münster Study Group. Leuk Lymphoma. 2015;56:814-6 pubmed publisherBin P, Liu S, Chen S, Zeng Z, Huang R, Yin Y, et al. The effect of aspartate supplementation on the microbial composition and innate immunity on mice. Amino Acids. 2017;49:2045-2051 pubmed publisher..5 and 1.0% Asp-supplemented groups. Dietary supplementation with 2.0% Asp enhanced the expression of pIgR and Crp1 as compared to the other three groups. The results indicated that dietary 1...Peyrouze P, Guihard S, Grardel N, Berthon C, Pottier N, Pigneux A, et al. Genetic polymorphisms in ARID5B, CEBPE, IKZF1 and CDKN2A in relation with risk of acute lymphoblastic leukaemia in adults: a Group for Research on Adult Acute Lymphoblastic Leukaemia (GRAALL) study. Br J Haematol. 2012;159:599-602 pubmed publisherCai R, Cai X, Chen B, Xu W, Lu J. C/EBP? participates in all-trans retinoic acid induction of PI3K? in U937 cells via an intronic matrix attachment region sequence. Mol Biol Rep. 2010;37:3795-800 pubmed publisher..The results above collectively show that C/EBP? participates in ATRA induction of PI3K?. ..Nakka P, Archer N, Xu H, Lupo P, Raphael B, Yang J, et al. Novel Gene and Network Associations Found for Acute Lymphoblastic Leukemia Using Case-Control and Family-Based Studies in Multiethnic Populations. Cancer Epidemiol Biomarkers Prev. 2017;26:1531-1539 pubmed publisher..i>Cancer Epidemiol Biomarkers Prev; 26(10); 1531-9. ©2017 AACR. ..Al Absi B, Razif M, Noor S, Saif Ali R, Aqlan M, Salem S, et al. Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population. Genet Test Mol Biomarkers. 2017;21:592-599 pubmed publisher..The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children. ..Du J, Stankiewicz M, Liu Y, Xi Q, Schmitz J, Lekstrom Himes J, et al. Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein. J Biol Chem. 2002;277:43481-94 pubmed..The CCAAT enhancer binding protein epsilon (C/EBPepsilon) is expressed as multiple isoforms and has been shown to be essential to myeloid (..Bello Perez M, Falco A, Medina Gali R, Pereiro P, Encinar J, Novoa B, et al. Neutralization of viral infectivity by zebrafish c-reactive protein isoforms. Mol Immunol. 2017;91:145-155 pubmed publisherThis work explores the unexpected in vivo and in vitro anti-viral functions of the seven c-reactive protein (crp1-7) genes of zebrafish (Danio rerio)...Gombart A, Grewal J, Koeffler H. ATF4 differentially regulates transcriptional activation of myeloid-specific genes by C/EBPepsilon and C/EBPalpha. J Leukoc Biol. 2007;81:1535-47 pubmed..We propose that ATF4 may regulate myeloid gene expression differentially by potentiating C/EBPepsilon but inhibiting C/EBPalpha-mediated transcriptional activation. ..Khanna Gupta A, Sun H, Zibello T, Lee H, Dahl R, Boxer L, et al. Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C/EBPepsilon gene. Blood. 2007;109:4181-90 pubmed..We hypothesize that decreased Gfi-1 levels in our SGD patient, together with the mutant C/EBPepsilon, block SGP expression, thereby contributing to the underlying etiology of the disease in our patient. ..Newman J, Keating A. Comprehensive identification of human bZIP interactions with coiled-coil arrays. Science. 2003;300:2097-101 pubmed..Biophysical studies in solution support the relative binding strengths observed with the arrays. New associations provide insights into the circadian clock and the unfolded protein response. ..Khanna Gupta A, Zibello T, Sun H, Gaines P, Berliner N. Chromatin immunoprecipitation (ChIP) studies indicate a role for CCAAT enhancer binding proteins alpha and epsilon (C/EBP alpha and C/EBP epsilon ) and CDP/cut in myeloid maturation-induced lactoferrin gene expression. Blood. 2003;101:3460-8 pubmed..We conclude that C/EBP alpha, C/EBP epsilon, and CDP/cut all play definitive roles in regulating late gene expression during normal myeloid development. ..Gombart A, Kwok S, Anderson K, Yamaguchi Y, Torbett B, Koeffler H. Regulation of neutrophil and eosinophil secondary granule gene expression by transcription factors C/EBP epsilon and PU.1. Blood. 2003;101:3265-73 pubmed..Furthermore, it indicates the importance of PU.1 in the cooperative activation of eosinophil granule genes. ..Gombart A, Koeffler H. Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C/EBP(epsilon). Curr Opin Hematol. 2002;9:36-42 pubmed..Deficiencies in multiple myeloid lineages, in addition to neutrophils, indicate the importance of C/EBP(epsilon) in regulating important innate immune and inflammatory responses critical for host defense. ..Verbeek W, Gombart A, Chumakov A, Muller C, Friedman A, Koeffler H. C/EBPepsilon directly interacts with the DNA binding domain of c-myb and cooperatively activates transcription of myeloid promoters. Blood. 1999;93:3327-37 pubmed..These results demonstrate a role for C/EBPepsilon in regulating myeloid promoters, such as neutrophil elastase, probably through a direct interaction with c-myb. ..Sladek F, Darnell J. Mechanisms of liver-specific gene expression. Curr Opin Genet Dev. 1992;2:256-9 pubmed..Analyses of the promoter regions of several factors have also been initiated and Drosophila homologs for two of these factors have been found, opening the way for studies on development. ..Mejri A, Mansri M, Hadj Fredj S, Ouali F, Bibi A, Hafsia R, et al. First description of the rs45496295 polymorphism of the C/EBPE gene in ?-thalassemia intermedia patients. Hemoglobin. 2016;40:411-416 pubmed publisher..The T allele of rs45496295, associated with moderate type of ?-thal, seems to modify the C/EBP? action, thereby preventing the hemolysis. ..Kim J, Cantwell C, Johnson P, Pfarr C, Williams S. Transcriptional activity of CCAAT/enhancer-binding proteins is controlled by a conserved inhibitory domain that is a target for sumoylation. J Biol Chem. 2002;277:38037-44 pubmed..SUMO-1 attachment decreased the inhibitory effect of the C/EBP epsilon regulatory domain, suggesting that sumoylation may play an important role in modulating C/EBP epsilon activity as well as that of the other C/EBP family members. ..Wang C, Chen J, Sun H, Sun L, Liu Y. CEBPE polymorphism confers an increased risk of childhood acute lymphoblastic leukemia: a meta-analysis of 11 case-control studies with 5,639 cases and 10,036 controls. Ann Hematol. 2015;94:181-5 pubmed publisher..01) and B hyperdiploid ALL risk (ORâ€‰=â€‰1.84, 95Â % CI 1.40-2.43, Pâ€‰<â€‰0.01). This meta-analysis demonstrated that the CEBPE rs2239633 polymorphism was significantly associated with childhood ALL risk. ..Reddy K, Serio K, Hodulik C, Bigby T. 5-lipoxygenase-activating protein gene expression. Key role of CCAAT/enhancer-binding proteins (C/EBP) in constitutive and tumor necrosis factor (TNF) alpha-induced expression in THP-1 cells. J Biol Chem. 2003;278:13810-8 pubmed..We conclude that the FLAP gene is transactivated by members of the C/EBP family of transcription factors in inflammatory cells and that these factors play an important role in FLAP gene induction by TNFalpha. ..Gery S, Gombart A, Fung Y, Koeffler H. C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis. Blood. 2004;103:828-35 pubmedb>CCAAT enhancer binding protein epsilon (C/EBPepsilon) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation...Iriyama N, Yuan B, Yoshino Y, Hatta Y, Horikoshi A, Aizawa S, et al. Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid. Int J Oncol. 2014;44:865-73 pubmed publisher..Therefore, these results may provide novel insights into a possible combinational therapeutic approach for APL patients. ..Dimberg A, Kårehed K, Nilsson K, Oberg F. Inhibition of monocytic differentiation by phosphorylation-deficient Stat1 is associated with impaired expression of Stat2, ICSBP/IRF8 and C/EBPepsilon. Scand J Immunol. 2006;64:271-9 pubmedChokkalingam A, Hsu L, Metayer C, Hansen H, Month S, Barcellos L, et al. Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics. Cancer Causes Control. 2013;24:1789-95 pubmed publisher..Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors. ..Ryoo H, Kong M, Kim Y, Lee C. Identification of functional nucleotide and haplotype variants in the promoter of the CEBPE gene. J Hum Genet. 2013;58:600-3 pubmed publisher..As a result, a person with the allele or the corresponding haplotype might have increased susceptibility to ALL. Further research is warranted to investigate this hypothesis and the underlying mechanisms. ..Pierini V, Nofrini V, La Starza R, Barba G, Vitale A, Di Raimondo F, et al. Double CEBPE-IGH rearrangement due to chromosome duplication and cryptic insertion in an adult with B-cell acute lymphoblastic leukemia. Cancer Genet. 2011;204:563-8 pubmed publisher..Our findings confirm that deregulated CEBPE plays a crucial role in the pathogenesis of CEBPE-IGH positive B-ALL. ..Chumakov A, Silla A, Williamson E, Koeffler H. Modulation of DNA binding properties of CCAAT/enhancer binding protein epsilon by heterodimer formation and interactions with NFkappaB pathway. Blood. 2007;109:4209-19 pubmed..We suggest that interaction of the activated NFkappaB pathway and C/EBP-epsilon may be important in selective activation of a subset of C/EBP-epsilon-responsive genes. ..Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, te Kronnie G, Cario G, et al. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. Leukemia. 2012;26:902-9 pubmed publisher..The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis. ..Lekstrom Himes J, Dorman S, Kopar P, Holland S, Gallin J. Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon. J Exp Med. 1999;189:1847-52 pubmedYoshida H, Ichikawa H, Tagata Y, Katsumoto T, Ohnishi K, Akao Y, et al. PML-retinoic acid receptor alpha inhibits PML IV enhancement of PU.1-induced C/EBPepsilon expression in myeloid differentiation. Mol Cell Biol. 2007;27:5819-34 pubmed..1/PML IV/p300 complex and inhibited PU.1-induced transcription. These results suggest a novel pathogenic mechanism of the PML-retinoic acid receptor alpha fusion protein in acute promyelocytic leukemia. ..Tavor S, Vuong P, Park D, Gombart A, Cohen A, Koeffler H. Macrophage functional maturation and cytokine production are impaired in C/EBP epsilon-deficient mice. Blood. 2002;99:1794-801 pubmed..Taken together, this study implicates the C/EBP epsilon gene as an important transcription factor required for normal function and development of macrophages. ..Tanaka M, Gombart A, Koeffler H, Shiohara M. Expression of bactericidal/permeability-increasing protein requires C/EBP epsilon. Int J Hematol. 2007;85:304-11 pubmed..Expression of BPI in human cord blood cells was increased by incubation with 10-7 MATRA for 48 hours. These results demonstrate the requirement for C/EBP epsilon in mediating BPI gene expression in myeloid cells in vitro and in vivo. ..Truong B, Lee Y, Lodie T, Park D, Perrotti D, Watanabe N, et al. CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia. Blood. 2003;101:1141-8 pubmed..Our results support the hypothesis that induction of C/EBP activity is a critical effect of tRA in APL. Furthermore, our findings suggest that targeted modulation of C/EBP activities could provide a new approach to therapy of AML. ..Wada T, Akagi T, Muraoka M, Toma T, Kaji K, Agematsu K, et al. A Novel In-Frame Deletion in the Leucine Zipper Domain of C/EBPÎµ Leads to Neutrophil-Specific Granule Deficiency. J Immunol. 2015;195:80-6 pubmed publisher..These results further support the importance of the leucine zipper domain of C/EBPÎµ for its essential function, and indicate that multiple molecular mechanisms lead to SGD. ..Cloutier A, Guindi C, Larivee P, Dubois C, Amrani A, McDonald P. Inflammatory cytokine production by human neutrophils involves C/EBP transcription factors. J Immunol. 2009;182:563-71 pubmed..This is the first demonstration that C/EBP factors are important regulators of cytokine expression in human neutrophils. ..Gombart A, Shiohara M, Kwok S, Agematsu K, Komiyama A, Koeffler H. Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein--epsilon. Blood. 2001;97:2561-7 pubmed..This study strongly implicates mutation of the C/EBPepsilon gene as the primary genetic defect involved in the development of neutrophil SGD and defines its mechanism of inheritance. ..Priam P, Krasteva V, Rousseau P, D Angelo G, Gaboury L, Sauvageau G, et al. SMARCD2 subunit of SWI/SNF chromatin-remodeling complexes mediates granulopoiesis through a CEBP? dependent mechanism. Nat Genet. 2017;49:753-764 pubmed publisher..Strikingly, both CEBPE and SMARCD2 loss-of-function mutations identified in patients with SGD abolish the interaction with SWI/SNF and thereby secondary granule gene expression, thus providing a molecular basis for this disease. ..Migliorini G, Fiege B, Hosking F, Ma Y, Kumar R, Sherborne A, et al. Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype. Blood. 2013;122:3298-307 pubmed publisher..0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development. ..Bartels M, Govers A, Fleskens V, LourenÃ§o A, Pals C, Vervoort S, et al. Acetylation of C/EBPÎµ is a prerequisite for terminal neutrophil differentiation. Blood. 2015;125:1782-92 pubmed publisher..Taken together, our data illustrate a critical role for acetylation in the functional regulation of C/EBPÎµ activity during terminal neutrophil development. ..Hsu L, Chokkalingam A, Briggs F, Walsh K, Crouse V, Fu C, et al. Association of genetic variation in IKZF1, ARID5B, and CEBPE and surrogates for early-life infections with the risk of acute lymphoblastic leukemia in Hispanic children. Cancer Causes Control. 2015;26:609-19 pubmed publisher..Results implicate the ARID5B, CEBPE, and IKZF1 genes in the pathogenesis of childhood ALL. ..Sun J, Zheng J, Tang L, Healy J, Sinnett D, Dai Y. Association between CEBPE Variant and Childhood Acute Leukemia Risk: Evidence from a Meta-Analysis of 22 Studies. PLoS ONE. 2015;10:e0125657 pubmed publisher..Also, Begg's and Egger's tests did not indicate any evidence of obvious asymmetry. In summary, our study provided evidence that CEBPE rs2239633 variant is associated with decreased risk of childhood B-cell ALL in Europeans. ..Zhang P, Nelson E, Radomska H, Iwasaki Arai J, Akashi K, Friedman A, et al. Induction of granulocytic differentiation by 2 pathways. Blood. 2002;99:4406-12 pubmed