Ema H, Kitano K, Suda T, Sato Y, Muroi K, Ohta M, Yoshida M, Sakamoto S, Eguchi M, Miura Y
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Blood. 1990 Jan 15;75(2):350-6.
We demonstrated the significant eosinophilic growth of leukemic cells in the presence of interleukin-5 (IL-5) in 2 of 15 cases of acute myeloid leukemia. These two cases were M2 (FAB classification) with the translocation (8;21)(q22; q22). Bone marrow examination revealed the rather high percentages (6% and 9%) of atypical eosinophils in the total nucleated bone marrow cells in these two cases. In the remaining 13 cases, eosinophils were less than 2% in the nucleated bone marrow cells. In the methylcellulose culture system, 142 +/- 18 or 54 +/- 2 colonies were formed by 5 x 10(4) mononuclear cells in the presence of IL-5 in these two cases. These colonies mainly comprised mature eosinophils. Eosinophils were confirmed by Biebrich scarlet staining and electron microscopic examination using a specific lectin binding assay. The eosinophilic differentiation and proliferation of leukemic cells were also observed in the liquid culture system. It was shown that eosinophils observed in both systems were derived from leukemic cells using the chromosomal marker of leukemic cells, t(8;21). Leukemic cells also differentiated to neutrophils or both neutrophils and eosinophils in response to granulocyte colony-stimulating factor or interleukin-3, respectively, but did not respond noticeably to granulocyte-macrophage colony-stimulating factor. Although IL-5 acts on normal eosinophil committed precursors as a lineage-specific growth factor, at least some leukemic cells reacted to IL-5 and could proliferate and differentiate along eosinophilic pathway. Our findings suggest that atypical eosinophils observed in the bone marrow were derived from the leukemic clone in two cases of AML.
我们在15例急性髓系白血病患者中的2例中证实,在白细胞介素-5(IL-5)存在的情况下,白血病细胞有显著的嗜酸性粒细胞生长。这两例为M2型(FAB分类),伴有(8;21)(q22;q22)易位。骨髓检查显示,这两例患者骨髓有核细胞中异常嗜酸性粒细胞的比例相当高(分别为6%和9%)。其余13例患者骨髓有核细胞中嗜酸性粒细胞少于2%。在甲基纤维素培养系统中,这两例患者的5×10⁴个单核细胞在IL-5存在的情况下分别形成了142±18或54±2个集落。这些集落主要由成熟嗜酸性粒细胞组成。通过比布里希猩红染色和使用特异性凝集素结合试验的电子显微镜检查证实了嗜酸性粒细胞。在液体培养系统中也观察到了白血病细胞的嗜酸性分化和增殖。利用白血病细胞的染色体标志物t(8;21)表明,在两个系统中观察到的嗜酸性粒细胞均来源于白血病细胞。白血病细胞分别对粒细胞集落刺激因子或白细胞介素-3反应,分化为中性粒细胞或同时分化为中性粒细胞和嗜酸性粒细胞,但对粒细胞-巨噬细胞集落刺激因子无明显反应。尽管IL-5作为一种谱系特异性生长因子作用于正常嗜酸性粒细胞定向祖细胞,但至少一些白血病细胞对IL-5有反应,并能沿嗜酸性粒细胞途径增殖和分化。我们的研究结果表明,在两例急性髓系白血病患者的骨髓中观察到的异常嗜酸性粒细胞来源于白血病克隆。