The role of GATA-3 in T-cell lymphomas

描述（由申请人提供）：t细胞淋巴瘤约占所有非霍奇金淋巴瘤的10%，是异质性的，知之甚少，通常与预后不良有关。大多数t淋巴细胞增生性疾病的起源细胞仍然难以捉摸，这是该领域进一步发展的障碍。正常T细胞在特定转录因子的影响下，在抗原刺激下分化成功能不同的群体。例如，gata结合蛋白3 （GATA-3）是一种控制T细胞向辅助性T细胞2 （Th2）细胞分化的转录因子。我们有

DESCRIPTION (provided by applicant): The T-cell lymphomas, representing approximately 10% of all non-Hodgkin lymphomas, are heterogeneous, poorly understood, and generally associated with a dismal prognosis. The cell of origin for most T-cell lymphoproliferative disorders has remained elusive and represents a barrier to further advances in this field. Normal T cells, under the influence of specific transcription factors, differentiate into functionally disinct populations following antigenic stimulation. For example, GATA-binding protein 3 (GATA-3) is a transcription factor that controls T-cell differentiation into T helper type 2 (Th2) cells. We have shown that myeloid-derived cells are regulated by cytokines transcriptionally regulated by GATA-3 and that these cells, including lymphoma-associated macrophages, promote the growth and survival of malignant T cells. Therefore, we hypothesized that a subset of T-cell lymphomas may be Th2-cell derived and regulate their microenvironment by producing cytokines that are transcriptionally regulated by GATA-3. In support of this hypothesis, we have found that a subset of T-cell lymphomas with an especially poor prognosis expresses GATA-3 and that its expression is associated with clinical and biologic characteristics resembling Th2 cells. Therefore, we aim to test the hypothesis that GATA-3 expression identifies a previously uncharacterized subset of T-cell lymphomas that exploit a GATA-3 driven transcriptional program to regulate lymphoma-associated macrophages within the tumor microenvironment. This hypothesis may support a novel paradigm in tumor biology with implications that extend beyond the T-cell lymphomas. Namely, transcriptional programs that determine cell lineage and differentiation in malignant cells may regulate stromal cells within the tumor microenvironment that are required for tumor growth.