Coupling of growth and differentiation in normal myeloid precursors and the breakdown of this coupling in leukemia
Coupling of growth and differentiation in normal myeloid precursors and the breakdown of this coupling in leukemia
复制标题
正常骨髓前体细胞生长和分化的耦合以及白血病中这种耦合的破坏
DOI：
10.1002/ijc.2910320120
复制
发表时间：
1983
影响因子：
6.4
通讯作者：
L. Sachs
中科院分区：
文献类型：
--
作者：
J. Lotem;L. Sachs
正常的髓系前体依赖巨噬细胞和粒细胞生长诱导蛋白MGI-I来维持细胞的存活和增殖。MGI-I还诱导分化诱导蛋白MGI-2的产生，这种由生长诱导蛋白诱导的分化诱导蛋白为生长和分化的正常耦合提供了一种机制。结果表明，MGI-I对MGI-2的诱导作用发生在骨髓前体细胞中，而不存在于正常骨髓的其他细胞中，在加入MGI-I后6h即可检测到MGI-2的诱导，纯化的MGI-I可在这些细胞中诱导出MGI-2。但在MGI-2诱导分化后，这种对MGI-I的需求可以恢复。在这些分化的白血病细胞和正常髓系前体细胞中，需要相似浓度的MGI-I才能最佳地诱导生长。在MGI-I的存在下，这些分化的白血病细胞增殖，然后失去与分化相关的特性。与正常髓系细胞相比，MGI-I在需要分化的髓系白血病细胞中不诱导MGI-2。在有血清或无血清培养的细胞中，MGI-I缺乏对MGI-2的诱导，这可以解释分化相关特性的丧失。结果表明，在这些白血病细胞中，生长和分化之间的正常耦合机制已经遗传崩溃，因此MGI-I不再能诱导MGI-2。
Normal myeloid precursors are dependent on the macrophage and granulocyte growth‐inducing protein MGI‐I for cell viability and multiplication. MGI‐I also induces production of the differentiation‐inducing protein MGI‐2, and this induction of a differentiation‐inducing protein by a growth‐inducing protein provides a mechanism for the normal coupling of growth and differentiation. It is shown that this induction of MGI‐2 by MGI‐I occurs in the myeloid precursors and not in some other cells in the normal bone marrow, that the induced MGI‐2 can be detected 6 h after the addition of MGI‐I, and that MGI‐2 can be induced in these cells by purified MGI‐I. There are clones of myeloid leukemic cells that no longer require MGI‐I for cell viability and multiplication, but in which this requirement for MGI‐I can be restored after induction of differentiation by MGI‐2. A similar concentration of MGI‐I was required for the optimum induction of growth in these differentiating leukemic cells and in normal myeloid precursors. In the presence of MGI‐I these differentiating leukemic cells multiplied and then lost their differentiation‐associated properties. In contrast to normal myeloid cells, MGI‐I did not induce MGI‐2 in the MGI‐I requiring differentiating myeloid leukemic cells. This lack of induction of MGI‐2 by MGI‐I occurred in cells cultured in serum‐containing or serum‐free‐medium, and can explain the loss of differentiation‐associated properties. The results indicate that there has been a genetic breakdown of the normal coupling mechanism between growth and differentiation in these leukemic cells so that MGI‐I can no longer induce MGI‐2.
小鼠浆细胞瘤中非免疫球蛋白相关的 DNA 重排。
DOI：
10.1073/pnas.79.13.4175
发表时间：
1982
影响因子：
11.1
作者：
Harris,LJ;Lang,RB;Marcu,KB
通讯作者：
Marcu,KB