GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes.[5] It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming, lympathic system-forming, and other tissue-forming stem cells. GATA2 is encoded by the GATA2 gene, a gene which often suffers germline and somatic mutations which lead to a wide range of familial and sporadic diseases, respectively. The gene and its product are targets for the treatment of these diseases.[6][7]
Inactivating mutations of the GATA2 gene cause a reduction in the cellular levels of GATA2 and the development of a wide range of familial hematological, immunological, lymphatic, and/or other disorders that are grouped together into a common disease termed GATA2 deficiency. Less commonly, these disorders are associated with non-familial (i.e. sporadic or acquired) GATA inactivating mutations. GATA2 deficiency often begins with seemingly benign abnormalities but if untreated progresses to life-threatening opportunistic infections, virus-induced cancers, lung failure, the myelodysplastic syndrome (i.e. MDS), and/or acute myeloid leukemia, principally acute myeloid leukemia (AML), less commonly chronic myelomonocytic leukemia (CMML), and rarely a lymphoid leukemia.[6][7]
Overexpression of the GATA2 transcription factor that is not due to mutations in the GATA2 gene appears to be a secondary factor that promotes the aggressiveness of non-familial EVI1 positive AML as well as the progression of prostate cancer.[8][9][10][11]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000179348 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015053 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Lee ME, Temizer DH, Clifford JA, Quertermous T (25 August 1991). "Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells". J. Biol. Chem. 266 (24): 16188–92. doi:10.1016/S0021-9258(18)98533-9. PMID 1714909.
- ^ a b Crispino JD, Horwitz MS (April 2017). "GATA factor mutations in hematologic disease". Blood. 129 (15): 2103–2110. doi:10.1182/blood-2016-09-687889. PMC 5391620. PMID 28179280.
- ^ a b Hirabayashi S, Wlodarski MW, Kozyra E, Niemeyer CM (August 2017). "Heterogeneity of GATA2-related myeloid neoplasms". International Journal of Hematology. 106 (2): 175–182. doi:10.1007/s12185-017-2285-2. PMID 28643018.
- ^ Vicente C, Vazquez I, Conchillo A, García-Sánchez MA, Marcotegui N, Fuster O, González M, Calasanz MJ, Lahortiga I, Odero MD (March 2012). "Overexpression of GATA2 predicts an adverse prognosis for patients with acute myeloid leukemia and it is associated with distinct molecular abnormalities". Leukemia. 26 (3): 550–4. doi:10.1038/leu.2011.235. PMID 21904383.
- ^ Mir MA, Kochuparambil ST, Abraham RS, Rodriguez V, Howard M, Hsu AP, Jackson AE, Holland SM, Patnaik MM (April 2015). "Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations". Cancer Medicine. 4 (4): 490–9. doi:10.1002/cam4.384. PMC 4402062. PMID 25619630.
- ^ Rodriguez-Bravo V, Carceles-Cordon M, Hoshida Y, Cordon-Cardo C, Galsky MD, Domingo-Domenech J (January 2017). "The role of GATA2 in lethal prostate cancer aggressiveness". Nature Reviews. Urology. 14 (1): 38–48. doi:10.1038/nrurol.2016.225. PMC 5489122. PMID 27872477.
- ^ Obinata D, Takayama K, Takahashi S, Inoue S (February 2017). "Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate Cancer". Cancers. 9 (3): 22. doi:10.3390/cancers9030022. PMC 5366817. PMID 28264478.