Prenatal and postnatal myeloid cells demonstrate stepwise progression in the pathogenesis of MLL fusion gene leukemia
Prenatal and postnatal myeloid cells demonstrate stepwise progression in the pathogenesis of MLL fusion gene leukemia
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DOI：
10.1182/blood-2002-05-1515
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发表时间：
2003-04-15
期刊：
影响因子：
20.3
通讯作者：
Kersey, JH
中科院分区：
文献类型：
--
作者：
Johnson, JJ;Chen, WL;Kersey, JH
子宫内MLL（HRX，ALL-1）与人类伴侣基因融合后发生白血病的步骤则不是。知道的将MII-AF 9融合基因导入胚胎干细胞导致小鼠白血病，其细胞类型特异性类似于。人类在这项研究中，我们使用骨髓集落测定，免疫表型，和移植，以评估MII-AF 9小鼠骨髓。集落分析表明，出生前和出生后的MII-AF 9组织中CP 11b（+）/CD 117（+）/Gr-1（+/-）髓样细胞的数量显著增加，通常呈紧密簇状。产前髓系祖细胞的自我更新能力被发现减少后，一系列的集落形成细胞重新铺板。相比之下，出生后早期髓系祖细胞在重新接种后增加;然而，出生后早期髓系祖细胞的自我更新增强是有限的，并且不会导致体内长期细胞系或白血病。无限制的再接种，长期的CD 11b/Gr-1（+）骨髓细胞系，以及在移植实验中体内产生早期白血病的能力，仅在明显白血病的小鼠中发现。与野生型组织相比，产前MII-AF 9组织的总I（成熟和祖细胞）CD 11b/Gr-1+细胞减少。集落再铺板、免疫表型和细胞化学表明，从产前阶段开始的细胞分化的任何扰动都是部分的，并且在很大程度上是可逆的。我们描述了一个新的信息在体外和体内模型系统，允许研究MII融合基因白血病的发病机制的阶段，开始于产前髓系细胞，我进展到第二阶段，在出生后的时期，最后，在成年动物的显性白血病。(C)2003年，美国血液学会。
The steps to leukemia following an in utero fusion of MLL (HRX, ALL-1) to a partner gene in humans are not. known. introduction of the MII-AF9 fusion gene into embryonic stem cells results in leukemia in mice with cell-type specificity similar to. humans. In this study we used myeloid colony assays, immunophenotyping, and transplantation to evaluate myelopoiesis in MII-AF9 mice. Colony assays demonstrated that both prenatal and postnatal MII-AF9 tissues have significantly increased numbers of CP11b(+)/CD117(+)/Gr-1(+/-) myeloid cells, often in compact clusters. The self-renewal capacity of prenatal myeloid progenitors was found to decrease following serial replating of colony-forming cells. In contrast, early postnatal myeloid progenitors increased following replating; however, the enhanced self-renewal of early postnatal myeloid progenitor cells was limited and did not result in long-term cell, lines or leukemia in vivo. Unlimited replating, longterm CD11b/Gr-1(+) myeloid call lines, and the ability to produce early leukemia in Vivo in transplantation experiments, were found only in mice with overt leukemia. Prenatal MII-AF9 tissues had reduced total I (mature and progenitor) CD11b/Gr-1+ cells compared with wild-type tissues. Colony replating, immunophenotyping, and cytochemistry suggest that any perturbation of cellular differentiation from the prenatal stage onward is partial and largely reversible. We describe a no vel informative in vitro and in vivo model system that permits study of the stages in the pathogenesis of MII fusion gene leukemia, beginning in prenatal myeloid cells, I progressing to a second stage, in the postnatal period and, finally, resulting in overt leukemia in adult animals. (C) 2003 by The American Society of Hematology.