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重组粒细胞-巨噬细胞集落刺激因子和重组粒细胞集落刺激因子对急性髓细胞白血病原始祖细胞集落形成的影响。

Effect of recombinant GM-CSF and recombinant G-CSF on colony formation of blast progenitors in acute myeloblastic leukemia.

作者信息

Motoji T, Takanashi M, Fuchinoue M, Masuda M, Oshimi K, Mizoguchi H

机构信息

Department of Medicine, Tokyo Women's Medical College, Japan.

出版信息

Exp Hematol. 1989 Jan;17(1):56-60.

PMID:2783249
Abstract

The colony-promoting activities of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units [L-CFU]) from 21 patients with acute myeloblastic leukemia (AML) were examined using blast colony assay and compared to colony promotion stimulated by phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). Recombinant GM-CSF stimulated blast colonies in 13 out of 20 cases examined (1 case not done). The magnitude of stimulation by rGM-CSF varied significantly according to the type of AML, but in general was lower than that of PHA-LCM. Blast cells of type M1 did not form any colonies with rGM-CSF, although numerous colonies were produced with PHA-LCM. Type M4 blasts formed fairly large numbers of colonies, though slightly less than those stimulated by PHA-LCM. Blasts of type M2 and M5 formed colonies with the stimulation of rGM-CSF, but the numbers were considerably smaller than type M4 and those stimulated with PHA-LCM. Recombinant G-CSF stimulated blast colonies in only 5 out of 21 cases, 3 of them being type M2. The number of cases responding to rG-CSF was significantly smaller than that responding to rGM-CSF, and even in cases in which colonies were formed, the magnitude of stimulation was minimal. From these results it seems likely that blast cells of different types of AML require a different kind of CSF for their optimal growth; type M4 blasts responded to the stimulation of rGM-CSF well, but blasts of other types of AML responded poorly. Thus, except for type M4, CSF(s) other than rGM-CSF seems to be required for the sufficient growth of L-CFU. Recombinant G-CSF is not likely to play an essential role in the proliferation of leukemic blasts of most types. Previous exposure to rGM-CSF and rG-CSF did not alter the self-renewal capacity, cellular phenotype, and morphology of colony cells, indicating that the direction and degree of differentiation of L-CFU stimulated by rGM-CSF or rG-CSF were not different from those stimulated with PHA-LCM.

摘要

采用原始细胞集落测定法,检测了重组粒细胞 - 巨噬细胞集落刺激因子(rGM - CSF)和重组粒细胞集落刺激因子(rG - CSF)对21例急性髓细胞白血病(AML)患者原始祖细胞(白血病集落形成单位[L - CFU])的原发性和继发性集落形成的促集落活性,并与植物血凝素刺激的白细胞条件培养基(PHA - LCM)刺激的集落促进作用进行了比较。在检测的20例患者中,有13例(1例未检测)的重组GM - CSF刺激了原始细胞集落。rGM - CSF的刺激程度根据AML的类型有显著差异,但总体上低于PHA - LCM。M1型原始细胞在rGM - CSF作用下未形成任何集落,而PHA - LCM能产生大量集落。M4型原始细胞形成了相当数量的集落,尽管略少于PHA - LCM刺激产生的集落。M2型和M5型原始细胞在rGM - CSF刺激下形成了集落,但数量明显少于M4型以及PHA - LCM刺激产生的集落。重组G - CSF仅在21例中的5例刺激了原始细胞集落,其中3例为M2型。对rG - CSF有反应的病例数明显少于对rGM - CSF有反应的病例数,而且即使在形成集落的病例中,刺激程度也很轻微。从这些结果来看,不同类型AML的原始细胞可能需要不同类型的集落刺激因子来实现最佳生长;M4型原始细胞对rGM - CSF的刺激反应良好,但其他类型AML的原始细胞反应较差。因此,除M4型外,L - CFU的充分生长可能需要rGM - CSF以外的集落刺激因子。重组G - CSF在大多数类型白血病原始细胞的增殖中不太可能发挥重要作用。先前接触rGM - CSF和rG - CSF并未改变集落细胞的自我更新能力、细胞表型和形态,这表明rGM - CSF或rG - CSF刺激的L - CFU的分化方向和程度与PHA - LCM刺激的并无不同。

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