Genetic Analysis of Polarity

摘要： 人类和果蝇血液系统的发育机制显示 惊人的相似之处。大多数基因对细胞的形成和成熟是必不可少的 果蝇的血细胞在人类中是保守的，大多数与 恶性血液病。 我们已经发现了一个新的基因zfrp8，它控制着细胞的增殖。 造血器官，淋巴腺。Zfrp8基因中几个功能丧失的等位基因 淋巴腺的巨大增生，未成熟血细胞的过度增殖， 以及其他组织中严重的生长延迟。 Zfrp8与其人类同源基因PDCD2有50%的同源性。出现PDCD2 与人类血液恶性肿瘤有牵连。这一结论是基于其规律性的。 BCL6(B细胞淋巴瘤6)癌基因及其染色体定位 位于染色体6q27，在人类淋巴瘤中经常缺失。在一些淋巴瘤中， PDCD2存在于正常淋巴细胞的胞浆中，但在 恶性淋巴细胞，表明该基因在细胞中可能具有类似的功能 果蝇和人类的增殖。 在白血病患者的骨髓和血液中，我们检测到了较小的 比正常形式的PDCD2，即PDCD2？33，在健康人的样本中检测不到 控制。在我们测试的所有癌细胞系中都发现了PDCD2？33，因此 与细胞增殖和肿瘤形成水平的增加有关。因为 果蝇PDCD2/zfrp8功能丧失表型，血细胞高度增殖， 而PDCD2？33在恶性组织中的高表达，我们认为 PDCD2？33代表该蛋白的一种异常/致癌形式。 我们的实验旨在确定zfrp8在正常淋巴中的功能。 果蝇的腺体发育和其他组织的生长及其特征 其他基因，其中一些我们已经确定，与zfrp8一起发挥作用。我们 还建议定义脊椎动物中PDCD2的基因产物，并研究 它们在正常和恶性细胞中的功能。

Abstract: The developmental mechanisms of human and Drosophila blood systems show remarkable parallels. Most genes essential for the formation and maturation of Drosophila hemocytes are conserved in humans, and the majority is associated with hematopoietic malignancies. We have identified a new gene, zfrp8, controlling cell proliferation of the hematopoietic organs, the lymph glands. Several loss-of-function alleles in zfrp8 cause enormous hyperplasia of the lymph glands, over-proliferation of immature blood cells, and severe growth delay in other tissues. Zfrp8 and its human ortholog, PDCD2, are >50% homologous. PDCD2 appears to be involved in human blood malignancies. This conclusion is based on its regulation by the BCL6 (B-cell lymphoma 6) oncogene and its chromosomal localization to a region of chromosome 6q27, frequently deleted in human lymphomas. In some lymphomas, PDCD2 is present in the cytoplasm of normal lymphocytes, but is not detected in malignant lymphocytes, indicating that the gene may have similar function in cell proliferation in Drosophila and humans. In the bone marrow and blood of leukemia patients, we have detected a smaller than normal form of PDCD2, PDCD2?33, that is not detected in samples from healthy controls. PDCD2?33 is found in all the cancer cell lines we have tested and thus correlates with increased levels of cell proliferation and oncogenesis. Because of the Drosophila PDCD2/zfrp8 loss-of-function phenotype, strong hyperplasia of hemocytes, and the high level of expression of PDCD2?33 in malignant tissues, we propose that PDCD2?33 represents an abnormal/oncogenic form of the protein. Our experiments are aimed at defining the function of zfrp8 in normal lymph gland development and in growth of other tissues in Drosophila, and at characterizing additional genes, a few of which we have already identified, functioning with zfrp8. We also propose to define the gene products of PDCD2 in vertebrates, and to investigate their function in normal and malignant cells.