| Note | |
| | |
| Entity | DCML deficiency |
| Disease | Immunodeficiency syndrome associated with loss of dendritic cells, monocytes, B and NK cells, leading to the increasing incidence of mycobacterial, fungal and viral infections. This disease occurs sporadically or in an autosomal dominant inheritance with incomplete penetrance. Patients with DCML deficiency have high incidence of developing hematopoietic malignancies. DCML deficiency with mycobacterium avium complex infection has been described as "monoMAC (monocytopenia with Mycobacterium avium complex) syndrome". |
| Prognosis | Prone to develop MDS and AML. |
| | |
| | |
| Entity | Emberger syndrome |
| Disease | Sporadic or autosomal dominant disease with incomplete penetrance, which has a characteristic feature of primary lymphoedema with myelodysplasia. The lymphedema generally confined to the lower limbs and genitals. |
| Prognosis | Prone to develop AML. |
| | |
| | |
| Entity | 3q21q26 syndrome |
| Disease | Hematopoietic malignancies, including MDS and AML, caused by a chromosomal aberration between the regions 3q21 and 3q26. The 77-kbp upstream region of GATA2 gene on 3q21 is rearranged proximal to the Evi1 locus on 3q26 by the translocation or inversion. Aberrant expression of EVI1 gene lead by the activity of GATA2 enhancer is appeared to be involved in the pathogenesis and poor prognosis of this disease. |
| Prognosis | Unfavorable prognosis. |
| Cytogenetics | inv(3)(q21q26), t(3;3)(q21;q26). |
| | |
| | |
| Entity | Acute promyelocytic leukaemia (APL) |
| Disease | GATA2 may be involved in APL leukemogenesis by physical interaction with the PML component of PML-RARa fusion or with the variant PLZF-RARa fusion, generated respectively by t(15;17) or t(11;17) translocation. |
| | |
| | |
| Entity | Myelodysplasic syndrome |
| Disease | GATA2 is expressed in MDS, but not in normal controls; the frequency of expression increases with the severity of dysplasia (100% in RAEB/RAEB-T). |
| | |
| | |
| Entity | Myeloid transformation of chronic myelooid leukemia CML |
| Disease | Out of 85 unselected cases of CML blast transformation, 9 showed a GATA2 mutation: 8 with a T-->G substitution at aa359 in ZF2 (L359V) and 1 with a 6 aa deletion (aa 341 to 346) in ZF1. All 9 transformations were myeloid, with a myeloblastic or monoblastic morphology. L359V leads to a gain of function of GATA2 protein. |
| | |
| | |
| Entity | Aplastic anemia (AA) |
| Disease | Hypothetical. In knockout mice, GATA2 haploinsufficiency leads to a decrease of hematopoietic stem cells number and efficiency. In human, GATA2 mRNA expression is largely reduced in patients with AA. |
| | |
| | |
| Entity | Prostate cancer |
| Disease | High expression of GATA2 is associated with aggressiveness, high metastasis ratio and resistance for therapy in prostate cancer through, in part, the activation of androgen-receptor target genes in ligand-independent pathway. |
| Prognosis | Unfavorable prognosis. |
| | |
| | |
| Entity | Non-small cell lung cancer |
| Disease | GATA2 is required for the survival of Ras-mediated NSCLC by controlling IL-1/NF-κB signaling. Knockdown of GATA2 expression lead to a reduction of tumor burden in mouse model of NSCLC, suggesting that GATA2 is a therapeutic target of Ras mutant cancers. |
| | |
| | |
| Entity | Glioma |
| Disease | The level of GATA2 expression that might be regulated by EGFR/ERK signaling pathway is correlated with prognosis of glioma patients. |
| | |
| | |
| Entity | Neuroblastoma |
| Disease | The expression level of GATA2 is reverse-correlated with aggressiveness, as GATA2 may negatively regulate proliferation of neuroblastoma cells. |
| | |
| | |
| Entity | Renal cell carcinoma (RCC) |
| Disease | The expression level of GATA2 is reverse-correlated with aggressiveness, possibility of metastasis, and risk of recurrence in clear cell RCC. |
| | |
| | |
| Entity | Hepatocellular carcinoma |
| Disease | The expression level of GATA2 is reverse-correlated with poor prognosis of hepatocellular carcinoma. Knockdown of GATA2 expression enhances the proliferation of a human liver cancer cell line in vitro. |
| | |
| | |
| Entity | Colorectal cancer |
| Disease | High level of GATA2 expression is correlated with aggressive feature, high recurrence rate and poor outcome of colorectal cancer. |
| | |
| | |
| Entity | Breast cancer |
| Disease | Roles of GATA2 in pathogenesis of breast cancer are contraversial. Reports describing that GATA2 level was increased in breast cancer showed that GATA2 might be related to tumor progression by repressing PTEN activity and/or promoting expression of aromatase gene, whereas another report showed that the expression GATA2 gene was silenced by aberrant hyper-methylation of GATA2 promoter region. |
| | |
| DNA methylation changes in murine breast adenocarcinomas allow the identification of candidate genes for human breast carcinogenesis |
| Acosta D, Suzuki M, Connolly D, Thompson RF, Fazzari MJ, Greally JM, Montagna C |
| Mamm Genome 2011 Apr;22(3-4):249-59 |
| PMID 21373886 |
| |
| A role for GATA-2 in transition to an aggressive phenotype in prostate cancer through modulation of key androgen-regulated genes |
| Böhm M, Locke WJ, Sutherland RL, Kench JG, Henshall SM |
| Oncogene 2009 Oct 29;28(43):3847-56 |
| PMID 19684615 |
| |
| Defining the functional boundaries of the Gata2 locus by rescue with a linked bacterial artificial chromosome transgene |
| Brandt W, Khandekar M, Suzuki N, Yamamoto M, Lim KC, Engel JD |
| J Biol Chem 2008 Apr 4;283(14):8976-83 |
| PMID 18211891 |
| |
| GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome |
| Fadilah SA, Cheong SK, Roslan H, Rozie-Hanisa M, Yen GK |
| Leukemia 2002 Aug;16(8):1563-5 |
| PMID 12145700 |
| |
| Decreased expression of transcription factor GATA-2 in haematopoietic stem cells in patients with aplastic anaemia |
| Fujimaki S, Harigae H, Sugawara T, Takasawa N, Sasaki T, Kaku M |
| Br J Haematol 2001 Apr;113(1):52-7 |
| PMID 11328281 |
| |
| A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia |
| Gröschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BA, Erpelinck C, van der Velden VH, Havermans M, Avellino R, van Lom K, Rombouts EJ, van Duin M, Döhner K, Beverloo HB, Bradner JE, Döhner H, Löwenberg B, Valk PJ, Bindels EM, de Laat W, Delwel R |
| Cell 2014 Apr 10;157(2):369-81 |
| PMID 24703711 |
| |
| GATA transcription factors and hematological diseases |
| Harigae H |
| Tohoku J Exp Med 2006 Sep;210(1):1-9 |
| PMID 16960339 |
| |
| GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes |
| Hoene V, Fischer M, Ivanova A, Wallach T, Berthold F, Dame C |
| Br J Cancer 2009 Oct 20;101(8):1481-9 |
| PMID 19707195 |
| |
| Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity |
| Johnson KD, Hsu AP, Ryu MJ, Wang J, Gao X, Boyer ME, Liu Y, Lee Y, Calvo KR, Keles S, Zhang J, Holland SM, Bresnick EH |
| J Clin Invest 2012 Oct;122(10):3692-704 |
| |
| GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells |
| Kamata M, Okitsu Y, Fujiwara T, Kanehira M, Nakajima S, Takahashi T, Inoue A, Fukuhara N, Onishi Y, Ishizawa K, Shimizu R, Yamamoto M, Harigae H |
| Haematologica 2014 Nov;99(11):1686-96 |
| PMID 25150255 |
| |
| A Gata2 intronic enhancer confers its pan-endothelia-specific regulation |
| Khandekar M, Brandt W, Zhou Y, Dagenais S, Glover TW, Suzuki N, Shimizu R, Yamamoto M, Lim KC, Engel JD |
| Development 2007 May;134(9):1703-12 |
| PMID 17395646 |
| |
| The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer |
| Kumar MS, Hancock DC, Molina-Arcas M, Steckel M, East P, Diefenbacher M, Armenteros-Monterroso E, Lassailly F, Matthews N, Nye E, Stamp G, Behrens A, Downward J |
| Cell 2012 Apr 27;149(3):642-55 |
| PMID 22541434 |
| |
| Decreased expression of GATA2 promoted proliferation, migration and invasion of HepG2 in vitro and correlated with poor prognosis of hepatocellular carcinoma |
| Li YW, Wang JX, Yin X, Qiu SJ, Wu H, Liao R, Yi Y, Xiao YS, Zhou J, Zhang BH, Fan J |
| PLoS One 2014 Jan 30;9(1):e87505 |
| PMID 24498120 |
| |
| Transcription factor GATA-2 is expressed in erythroid, early myeloid, and CD34+ human leukemia-derived cell lines |
| Nagai T, Harigae H, Ishihara H, Motohashi H, Minegishi N, Tsuchiya S, Hayashi N, Gu L, Andres B, Engel JD, et al |
| Blood 1994 Aug 15;84(4):1074-84 |
| PMID 7519472 |
| |
| Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome) |
| Ostergaard P, Simpson MA, Connell FC, Steward CG, Brice G, Woollard WJ, Dafou D, Kilo T, Smithson S, Lunt P, Murday VA, Hodgson S, Keenan R, Pilz DT, Martinez-Corral I, Makinen T, Mortimer PS, Jeffery S, Trembath RC, Mansour S |
| Nat Genet 2011 Sep 4;43(10):929-31 |
| PMID 21892158 |
| |
| Decreased mRNA expression of GATA1 and GATA2 is associated with tumor aggressiveness and poor outcome in clear cell renal cell carcinoma |
| Peters I, Dubrowinskaja N, Tezval H, Kramer MW, von Klot CA, Hennenlotter J, Stenzl A, Scherer R, Kuczyk MA, Serth J |
| Target Oncol 2015 Jun;10(2):267-75 |
| PMID 25230694 |
| |
| Cloning and characterization of a novel endothelial promoter of the human CYP19 (aromatase P450) gene that is up-regulated in breast cancer tissue |
| Sebastian S, Takayama K, Shozu M, Bulun SE |
| Mol Endocrinol 2002 Oct;16(10):2243-54 |
| PMID 12351690 |
| |
| Potentiation of GATA-2 activity through interactions with the promyelocytic leukemia protein (PML) and the t(15;17)-generated PML-retinoic acid receptor alpha oncoprotein |
| Tsuzuki S, Towatari M, Saito H, Enver T |
| Mol Cell Biol 2000 Sep;20(17):6276-86 |
| PMID 10938104 |
| |
| GATA2 negatively regulates PTEN by preventing nuclear translocation of androgen receptor and by androgen-independent suppression of PTEN transcription in breast cancer |
| Wang Y, He X, Ngeow J, Eng C |
| Hum Mol Genet 2012 Feb 1;21(3):569-76 |
| PMID 22021428 |
| |
| GATA2 promotes glioma progression through EGFR/ERK/Elk-1 pathway |
| Wang Z, Yuan H, Sun C, Xu L, Chen Y, Zhu Q, Zhao H, Huang Q, Dong J, Lan Q |
| Med Oncol 2015 Apr;32(4):87 |
| PMID 25707769 |
| |
| GATA-1, -2 and -3 genes expression in bone marrow microenviroment with chronic aplastic anemia |
| Wu X, Li Y, Zhu K, Wang Z, Chen S, Yang L |
| Hematology 2007 Aug;12(4):331-5 |
| PMID 17654061 |
| |
| Activity and tissue-specific expression of the transcription factor NF-E1 multigene family |
| Yamamoto M, Ko LJ, Leonard MW, Beug H, Orkin SH, Engel JD |
| Genes Dev 1990 Oct;4(10):1650-62 |
| PMID 2249770 |
| |
| A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression |
| Yamazaki H, Suzuki M, Otsuki A, Shimizu R, Bresnick EH, Engel JD, Yamamoto M |
| Cancer Cell 2014 Apr 14;25(4):415-27 |
| PMID 24703906 |
| |
| Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia |
| Zhang SJ, Ma LY, Huang QH, Li G, Gu BW, Gao XD, Shi JY, Wang YY, Gao L, Cai X, Ren RB, Zhu J, Chen Z, Chen SJ |
| Proc Natl Acad Sci U S A 2008 Feb 12;105(6):2076-81 |
| PMID 18250304 |
| |
