Bredoux C, Uphoff C C, Drexler H G
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Leuk Res. 1997 Jul;21(7):595-601. doi: 10.1016/s0145-2126(97)00014-3.
The tie gene encodes a receptor tyrosine kinase that together with its thus far unidentified ligand appears to play a distinct role in the regulatory pathway of early hematopoiesis and angiogenesis. Here, we attempted to define the possible involvement of tie in the pathobiology of hematopoietic malignancies by examining tie mRNA expression in human leukemia and lymphoma cells. We used a large panel of 93 well-characterized human continuous leukemia-lymphoma cell lines as model systems for the various hematopoietic cell lineages. At the Northern blot level, none of the 27 lymphoid leukemia or lymphoma-derived cell lines (originating from four B-precursor leukemia, four B-cell leukemia, four B-cell non-Hodgkin's lymphoma, two myeloma, two Burkitt lymphoma, four T-cell leukemia, five Hodgkin lymphoma, two anaplastic large cell lymphoma) tested expressed tie transcripts, whereas 23/42 (55%) of the myeloid cell lines analyzed expressed tie mRNA: in detail, 15 of 20 (75%) megakaryocytic, five of 11 (45%) erythroid, three of seven (43%) myelocytic and none of four monocytic cell lines were tie mRNA positive. In the reverse transcriptase-polymerase chain reaction analysis, which can detect very low levels of mRNA expression, all 12 myeloid cell lines and 19 of 39 (48%) lymphoid cell lines were positive. In experiments aimed at inducing cellular differentiation over an incubation period of 4 days, the phorbol ester PMA strongly enhanced tie mRNA expression in one erythroid and in one myelocytic cell line, but (like thrombopoietin) down-regulated tie mRNA expression in two megakaryocytic cell lines. Taken together these results indicate that tie is predominantly expressed in leukemia cells derived from the myeloid cell lineages (and here in particular in megakaryoblastic cells) and not in lymphoid leukemia cells. These observations provide some evidence for the hypothesis that tie is a receptor for a regulatory factor involved in normal and plausibly also leukemic hematopoiesis.
tie基因编码一种受体酪氨酸激酶，与其目前尚未明确的配体一起，似乎在早期造血和血管生成的调节途径中发挥独特作用。在此，我们试图通过检测人白血病和淋巴瘤细胞中tie mRNA的表达，来确定tie在造血系统恶性肿瘤病理生物学中的可能作用。我们使用了一组93个特征明确的人连续性白血病-淋巴瘤细胞系作为各种造血细胞谱系的模型系统。在Northern印迹水平上，所检测的27个淋巴样白血病或淋巴瘤来源的细胞系（源自4种B前体白血病、4种B细胞白血病、4种B细胞非霍奇金淋巴瘤、2种骨髓瘤、2种伯基特淋巴瘤、4种T细胞白血病、5种霍奇金淋巴瘤、2种间变性大细胞淋巴瘤）均未表达tie转录本，而在分析的42个髓样细胞系中有23个（55%）表达tie mRNA：具体而言，20个巨核细胞系中有15个（75%）、11个红系细胞系中有5个（45%）、7个髓细胞系中有3个（43%）表达tie mRNA，4个单核细胞系均未表达tie mRNA。在逆转录-聚合酶链反应分析中，该方法可检测到极低水平的mRNA表达，所有12个髓样细胞系以及39个淋巴样细胞系中的19个（48%）呈阳性。在旨在诱导细胞分化的4天孵育期实验中，佛波酯PMA强烈增强了一个红系细胞系和一个髓细胞系中的tie mRNA表达，但（与血小板生成素一样）下调了两个巨核细胞系中的tie mRNA表达。综合这些结果表明，tie主要在源自髓样细胞谱系的白血病细胞中表达（尤其在巨核母细胞中），而不在淋巴样白血病细胞中表达。这些观察结果为tie是参与正常以及可能也参与白血病造血的调节因子的受体这一假说提供了一些证据。
