Nagler A, Binet C, Mackichan M L, Negrin R, Bangs C, Donlon T, Greenberg P
Department of Medicine, Stanford University Medical Center, CA 94305.
Blood. 1990 Oct 1;76(7):1299-307.
Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics.
对36例骨髓增生异常综合征（MDS）患者（13例难治性贫血[RA]、14例伴有过多原始细胞的难治性贫血[RAEB]、9例转变中的RAEB[RAEB-T]）的骨髓细胞进行评估，观察其对重组人粒细胞集落刺激因子（G-CSF）或粒细胞-单核细胞集落刺激因子（GM-CSF）的体外增殖和分化反应。在这些患者中，GM-CSF对骨髓髓系克隆生长（CFU-GM）的增殖刺激作用强于G-CSF（每10⁵个非贴壁悬浮骨髓细胞[NAB]分别形成44个和12个集落，P<0.025）。与20例细胞遗传学正常的患者相比，GM-CSF刺激16例骨髓细胞遗传学异常的患者CFU-GM生长增加（每10⁵个NAB分别形成52个和30个集落，P<0.05），而G-CSF未显示出这种差异（每10⁵个NAB分别形成11个和16个集落）。相反，在液体培养中，G-CSF诱导32例患者中的15例（47%）骨髓细胞发生粒细胞分化，而GM-CSF仅诱导18例患者中的4例（22%）发生粒细胞分化（P<0.025），包括RAEB/RAEB-T患者：分别为18例中的9例和9例中的0例（P<0.025）。对于细胞遗传学正常的MDS患者，G-CSF和GM-CSF分别诱导18例中的12例（67%）和11例中的3例（27%）骨髓细胞发生粒细胞分化（P<0.025），而细胞遗传学异常的患者中分别只有14例中的3例（21%）和7例中的1例（14%）发生粒细胞诱导分化。我们得出结论，在体外，对于MDS骨髓细胞，G-CSF比GM-CSF具有更强的粒细胞分化活性和较弱的增殖活性，特别是对于RAEB/RAEB-T患者和细胞遗传学正常的患者。
