糖尿病对多发性骨髓瘤造血干细胞动员及骨髓巨噬细胞极化的影响

Effects of diabetes mellitus on mobilization of hematopoietic stem cells and bone marrow macrophage po-larization in multiple myeloma patients

目的：研究2型糖尿病（ T2DM）对多发性骨髓瘤干细胞动员效果的影响及机制。方法收集行造血干细胞（hematopoietic stem cells，HSCs）动员采集的多发性骨髓瘤（multiple myeloma，MM）患者48例，其中合并糖尿病（ DM）的MM患者15例，不合并DM的MM患者33例；男29例，女19例；中位年龄55.2（41～63）岁。观察2组采集的CD34＋细胞数量有无差异，检测2组骨髓CD11c阳性与CD206阳性细胞数，以2者比值即CD11 c／CD206数值代表骨髓巨噬细胞M1型／M2型，进一步探讨巨噬细胞极化状态与采集的CD34＋细胞数量的相关性。结果①MM患者采集CD34＋细胞数目为（4.63±1.75）×10^6／kg，合并DM的MM患者采集CD34＋细胞数目为（3.12±1.84）×10^6／kg，MM组采集的CD34＋细胞数目明显高于合并DM的MM患者组（P＜0.05）。②MM患者CD11c／CD206细胞比值为1.42±0.16，合并DM的MM患者CD11c／CD206细胞比值为3.08±0.37，提示合并DM的MM患者骨髓MΦ发生M1型极化。③6例干细胞采集数＜2×10^6／kg的患者CD11c／CD206为2.87±0.42，14例＞2×106／kg干细胞采集数＜5×10^6／kg的患者CD11c／CD206为1.91±0.28，8例干细胞采集数＞5×106／kg的患者CD11c／CD206为1.48±0.25，3组差异均具有统计学意义（P＜0.05），提示巨噬细胞极化与干细胞采集数目之间可能具有相关性。结论 DM是多发性骨髓瘤干细胞动员采集的不利因素，其作用可能与DM促使骨髓巨噬细胞M1极化有关。

Objective To study the impact and mechanisms of type 2 diabetes mellitus（ T2DM） on mobi-lization of hematopoietic stem cells of multiple myeloma（ MM） .Methods 48 patients diagnosed with MM whose hematopoietic stem cells were collected entered the study, including 15 cases with DM, and 33 cases without DM.29 were males and 19 were females, with 55.2 as the median age, ranging from 41 to 63 years.We ob-served numbers of CD34 ＋cells collected, CD11c positive cells and CD206 positive cells in bone marrow, then the ratio of CD11c/CD206 was considered as the ratio of M1 macrophages/M2 macrophages, in the end we explored the relevance of macrophage polarization status with the number of CD34 ＋cells collected.Results ①The num-ber of CD34 ＋cells collected in MM patients was（4.63 ±1.75） ×106/kg, while the number in MM patients with DM was（3.12 ±1.84） ×106/kg.The number of CD34 ＋in MM group was significantly higher than that in the MM with DM group（P〈0.05）.②CD11c/CD206 cell ratio in MM patients was 1.42 ±0.16, while the ratio was 3.08 ±0.37 in MM patients with DM, indicating that MΦM1 polarization occurred in the MM with DM group.③CD11c/CD206 cell ratio was 2.87 ±0.42 in 6 patients whose stem cell collection number was less than 2 ×106/kg, the ratio was 1.91 ±0.28 in 14 patients whose stem cell collection number was between 2 ×106/kg and 5 × 106/kg, and the ratio was 1.48 ±0.25 in 8 patients whose stem cell collection number was more than 5 ×106/kg.There were significant differences in these 3 groups（ P〈0.05） , indicating that macrophage polarization and the number of stem cell collection was relevant.Conclusions DM is unfavorable factor in stem cell mobilization and collection of multiple myeloma, it may be related to macrophages M1 polarization induced by diabetes.