Kohmura Kanoko, Miyakawa Yoshitaka, Kameyama Kaori, Kizaki Masahiro, Ikeda Yasuo
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Leuk Lymphoma. 2004 Jul;45(7):1475-9. doi: 10.1080/10428190310001645870.
We report a case of IgG-kappa multiple myeloma associated with neutrophilia (WBC 31,300/microl, neutrophil 90.5%). Interestingly, the serum level of granulocyte colony stimulating factor (G-CSF) in this patient was elevated to 1,500 pg/ml (normal range: 5.78-27.5). Plasma cells were 35% in the bone marrow and were strongly stained with anti-G-CSF antibody. To directly study the production of G-CSF from plasma cells in this patient, CD138 positive plasma cells were purified from bone marrow of multiple myeloma patients by magnetic sorting. The expression of G-CSF mRNA was observed in CD138 positive plasma cells from this myeloma patient with neutrophilia by RT-PCR. In contrast, the expression of G-CSF mRNA was not detected in CD138 positive plasma cells from the other multiple myeloma patients without neutrophilia and 4 human myeloma cell lines (HS-Sultan, IM9, RPMI8226, U266) by RT-PCR. After the CD138 positive plasma cells were cultured in vitro for 48 h, the production of G-CSF protein was confirmed (71.8 pg/ml) in the supernatant by ELISA. These results indicated plasma cells of this myeloma patient directly produced G-CSF and that this was the primary cause of neutrophilia.
我们报告一例与嗜中性粒细胞增多相关的IgG-κ型多发性骨髓瘤病例(白细胞计数31,300/微升,中性粒细胞90.5%)。有趣的是,该患者血清粒细胞集落刺激因子(G-CSF)水平升高至1500 pg/ml(正常范围:5.78-27.5)。骨髓中浆细胞占35%,且用抗G-CSF抗体染色呈强阳性。为直接研究该患者浆细胞产生G-CSF的情况,通过磁珠分选从多发性骨髓瘤患者骨髓中纯化出CD138阳性浆细胞。通过逆转录聚合酶链反应(RT-PCR)在该伴有嗜中性粒细胞增多的骨髓瘤患者的CD138阳性浆细胞中观察到G-CSF mRNA的表达。相比之下,通过RT-PCR在其他无嗜中性粒细胞增多的多发性骨髓瘤患者的CD138阳性浆细胞以及4种人骨髓瘤细胞系(HS-Sultan、IM9、RPMI8226、U266)中未检测到G-CSF mRNA的表达。将CD138阳性浆细胞体外培养48小时后,通过酶联免疫吸附测定(ELISA)在上清液中证实有G-CSF蛋白产生(71.8 pg/ml)。这些结果表明该骨髓瘤患者的浆细胞直接产生G-CSF,这是嗜中性粒细胞增多的主要原因。