Dorfman David M, Morgan Elizabeth A, Pelton Ashley, Unitt Christine
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hum Pathol. 2017 Jul;65:166-174. doi: 10.1016/j.humpath.2017.05.009. Epub 2017 May 24.
T-cell transcription factor GATA-3, known to play a role in early T-cell development and in the development of T-cell neoplasms, is expressed at high levels in fetal and adult thymus, as well as in acute leukemias with T-cell differentiation, including T-lymphoblastic leukemia/lymphoma (22/22 cases), early T-cell precursor lymphoblastic leukemia (11/11 cases), and mixed-phenotype acute leukemia, T/myeloid (4/5 cases), but only rarely in acute myeloid leukemia/myeloid sarcoma (1/36 cases), and not in B-lymphoblastic leukemia (0/16 cases). In contrast, T-bet, the other T-cell transcription factor that controls Th1/Th2 T-cell fate, is not expressed to any significant extent in immature thymocytes or in cases of T-lymphoblastic leukemia or acute myeloid leukemia/myeloid sarcoma, but is expressed in most cases (15/16) of B-lymphoblastic leukemia and in mixed-phenotype acute leukemia, B/myeloid. GATA-3-positive acute leukemias with T-cell differentiation were also found to express proto-oncogene C-MYC, in an average of 52% of neoplastic cells, which, along with GATA-3, may contribute to leukemogenesis, as suggested by transgenic mouse models. We conclude that GATA-3 is a sensitive and specific marker for the diagnosis of acute leukemias with T-cell differentiation and may be a useful addition to the panel of immunophenotypic markers for the diagnostic evaluation of acute leukemias.
T细胞转录因子GATA-3在早期T细胞发育及T细胞肿瘤发生过程中发挥作用,在胎儿及成人胸腺中高表达,在伴有T细胞分化的急性白血病中也高表达,包括T淋巴细胞母细胞白血病/淋巴瘤(22/22例)、早期T细胞前体淋巴细胞白血病(11/11例)以及混合表型急性白血病T/髓系(4/5例),但在急性髓系白血病/髓系肉瘤中仅罕见表达(1/36例),在B淋巴细胞母细胞白血病中不表达(0/16例)。相比之下,另一个控制Th1/Th2 T细胞命运的T细胞转录因子T-bet在未成熟胸腺细胞、T淋巴细胞母细胞白血病或急性髓系白血病/髓系肉瘤病例中均无显著表达,但在大多数B淋巴细胞母细胞白血病病例(15/16)及混合表型急性白血病B/髓系中表达。伴有T细胞分化的GATA-3阳性急性白血病还被发现平均有52%的肿瘤细胞表达原癌基因C-MYC,如转基因小鼠模型所示,C-MYC与GATA-3可能共同促进白血病发生。我们得出结论,GATA-3是诊断伴有T细胞分化的急性白血病的敏感且特异的标志物,可能是急性白血病诊断评估免疫表型标志物组合中的有用补充。