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原发性人类成红细胞中巨核细胞分化的诱导:白血病谱系可塑性的生理基础。

Induction of megakaryocytic differentiation in primary human erythroblasts: a physiological basis for leukemic lineage plasticity.

作者信息

Goldfarb A N, Wong D, Racke F K

机构信息

Department of Pathology, University of Virginia Health Sciences Center, HSC Box 204, Charlottesville, VA 22908, USA.

出版信息

Am J Pathol. 2001 Apr;158(4):1191-8. doi: 10.1016/S0002-9440(10)64068-0.

DOI:10.1016/S0002-9440(10)64068-0
PMID:11290535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1891921/
Abstract

In myelodysplasias and acute myeloid leukemias, abnormalities in erythroid development often parallel abnormalities in megakaryocytic development. Erythroleukemic cells in particular have been shown to possess the potential to undergo megakaryocytic differentiation in response to a variety of stimuli. Whether or not such lineage plasticity occurs as a consequence of the leukemic phenotype has not previously been addressed. In this study, highly purified primary human erythroid progenitors were subjected to stimuli known to induce megakaryocytic differentiation in erythroleukemic cells. Remarkably, the primary erythroid progenitors rapidly responded with morphological and immunophenotypic evidence of megakaryocytic differentiation, equivalent to that seen in erythroleukemic cells. Even erythroblasts expressing high levels of hemoglobin manifested partial megakaryocytic differentiation. These results indicate that the lineage plasticity observed in erythroleukemic cells reflects an intrinsic property of cells in the erythroid lineage rather than an epiphenomenon of leukemic transformation.

摘要

在骨髓增生异常综合征和急性髓系白血病中,红系发育异常往往与巨核系发育异常并存。特别是红白血病细胞已被证明有潜力在多种刺激下发生巨核系分化。此前尚未探讨过这种谱系可塑性是否是白血病表型的结果。在本研究中,对高度纯化的原代人红系祖细胞施加已知可诱导红白血病细胞发生巨核系分化的刺激。值得注意的是,原代红系祖细胞迅速出现巨核系分化的形态学和免疫表型证据,与红白血病细胞中的情况相当。即使是表达高水平血红蛋白的成红细胞也表现出部分巨核系分化。这些结果表明,在红白血病细胞中观察到的谱系可塑性反映了红系谱系细胞的内在特性,而非白血病转化的附带现象。

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本文引用的文献

1
A potential role for protein kinase C-epsilon in regulating megakaryocytic lineage commitment.蛋白激酶C-ε在调节巨核细胞系定向分化中的潜在作用。
J Biol Chem. 2001 Jan 5;276(1):522-8. doi: 10.1074/jbc.M005236200.
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Blood. 2000 Apr 15;95(8):2559-68.
4
Protein kinase C-alpha isoform is involved in erythropoietin-induced erythroid differentiation of CD34(+) progenitor cells from human bone marrow.蛋白激酶C-α亚型参与促红细胞生成素诱导的人骨髓CD34(+)祖细胞的红系分化。
Blood. 2000 Jan 15;95(2):510-8.
5
Expression of CD41 and c-mpl does not indicate commitment to the megakaryocyte lineage during haemopoietic development.CD41和c-mpl的表达并不表明在造血发育过程中已定向分化为巨核细胞系。
Br J Haematol. 1999 Jun;105(4):1044-54. doi: 10.1046/j.1365-2141.1999.01446.x.
6
The expression of human blood group antigens during erythropoiesis in a cell culture system.人血型抗原在细胞培养系统中红细胞生成过程中的表达。
Blood. 1999 Jun 15;93(12):4425-35.
7
Apoptosis of erythroid precursors under stimulation with thrombopoietin: contribution to megakaryocytic lineage choice.血小板生成素刺激下红系前体细胞的凋亡:对巨核细胞谱系选择的作用
Stem Cells. 1999;17(1):45-53. doi: 10.1002/stem.170045.
8
Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo.血小板生成素和粒细胞集落刺激因子受体在体内造血细胞命运决定中的许可作用。
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):698-702. doi: 10.1073/pnas.96.2.698.
9
Coexpression of erythroid and megakaryocytic genes in acute erythroblastic (FAB M6) and megakaryoblastic (FAB M7) leukaemias.红系和巨核系基因在急性红白血病(FAB M6)和急性巨核细胞白血病(FAB M7)中的共表达。
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