Sakajiri S, O'kelly J, Yin D, Miller C W, Hofmann W K, Oshimi K, Shih L-Y, Kim K-H, Sul H S, Jensen C H, Teisner B, Kawamata N, Koeffler H P
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA, Los Angeles, CA 90048, USA.
Leukemia. 2005 Aug;19(8):1404-10. doi: 10.1038/sj.leu.2403832.
Dlk1 (Pref-1) is a transmembrane and secreted protein, which is a member of the epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We have found by real-time RT-PCR that Dlk1 mRNA levels were high in CD34(+) cells in 10 of 12 MDS samples compared with CD34(+) cells from 11 normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during megakaryocytic differentiation of both CMK megakaryoblasts as well as normal CD34(+) hematopoietic stem cells. High serum levels of Dlk1 occurred in RA (4/10) and essential thrombocythemia (2/10) patients. Functional studies showed that forced expression of Dlk1 enhanced proliferation of K562 cells growing in 1% fetal bovine serum. Analysis of hematopoiesis of Dlk1 knockout mice suggested that Dlk1 contributed to granulocyte, megakaryocyte and B-cell clonogenic growth and was needed for generation of splenic B-cells. In summary, Dlk1 is overexpressed in selected samples of MDS (especially RA and RAEB) and AML (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells.
Dlk1（Pref-1）是一种跨膜且可分泌的蛋白质，它是表皮生长因子样家族的成员，与Notch/Delta/Serrate同源。我们通过实时逆转录聚合酶链反应发现，与11名正常人的CD34(+)细胞相比，12例骨髓增生异常综合征（MDS）样本中有10例的CD34(+)细胞中Dlk1信使核糖核酸（mRNA）水平较高。此外，在38例MDS患者中的11例、11例急性髓系白血病（AML）M6中的5例以及4例AML M7样本中的2例的单核、低密度骨髓细胞中，Dlk1 mRNA也有所升高。此外，6例红白血病中的5例以及2例巨核细胞白血病细胞系均高表达Dlk1 mRNA。在CMK巨核母细胞以及正常CD34(+)造血干细胞的巨核细胞分化过程中，Dlk1 mRNA水平显著增加。类风湿性关节炎（RA）（4/10）和原发性血小板增多症（2/10）患者的血清Dlk1水平较高。功能研究表明，Dlk1的强制表达增强了在1%胎牛血清中生长的K562细胞的增殖。对Dlk1基因敲除小鼠造血功能的分析表明，Dlk1有助于粒细胞、巨核细胞和B细胞的克隆生长，并且是脾B细胞生成所必需的。总之，Dlk1在MDS（尤其是RA和难治性贫血伴原始细胞过多（RAEB））和AML（特别是M6、M7）的选定样本中过度表达，并且它似乎与巨核细胞和B细胞的正常发育有关。
