Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma
Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma
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DOI：
10.1038/leu.2010.320
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发表时间：
2011-04-01
期刊：
影响因子：
11.4
通讯作者：
Orfao, A.
中科院分区：
文献类型：
--
作者：
Paiva, B.;Perez-Andres, M.;Orfao, A.
正常骨髓（BM）浆细胞（PC）的消失预示着意义不明的单克隆丙种球蛋白病（MGUS）和郁积性骨髓瘤（SMM）向症状性多发性骨髓瘤（MM）的恶性转化。正常PC以及CD 34（+）造血干细胞（HSC）、B细胞前体和克隆PC的归巢、行为和存活在很大程度上取决于它们与表达基质细胞衍生因子-1（SDF-1）的、潜在地重叠BM基质细胞小生境的相互作用。在这里，我们研究了这些细胞群在MGUS、SMM和MM患者与年龄>60岁的健康成人（HA）中的分布、表型特征和竞争迁移能力。我们的研究结果表明，BM和外周血（PB）克隆PC从MGUS到MM逐渐增加，后者显示出稍微更不成熟的免疫表型。值得注意的是，这种克隆PC数量的增加与BM中正常PC、B细胞前体和CD 34（+）HSC的进行性消耗相关，也与PB的平行增加相关。在离体模型中，正常PC、B细胞前体和来自MGUS和SMM的CD 34（+）HSC（但MM患者不能）能够消除克隆PC迁移到系列浓度的SDF-1中。总体而言，我们的结果表明，克隆PC对正常BM细胞的进行性竞争和替代与MGUS、SMM和MM患者的更晚期疾病相关。Leukemia（2011）25，697-706; doi：10.1038/leu.2010.320; 2011年1月21日在线发表
Disappearance of normal bone marrow (BM) plasma cells (PC) predicts malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) into symptomatic multiple myeloma (MM). The homing, behavior and survival of normal PC, but also CD34(+) hematopoietic stem cells (HSC), B-cell precursors, and clonal PC largely depends on their interaction with stromal cell-derived factor-1 (SDF-1) expressing, potentially overlapping BM stromal cell niches. Here, we investigate the distribution, phenotypic characteristics and competitive migration capacity of these cell populations in patients with MGUS, SMM and MM vs healthy adults (HA) aged >60 years. Our results show that BM and peripheral blood (PB) clonal PC progressively increase from MGUS to MM, the latter showing a slightly more immature immunophenotype. Of note, such increased number of clonal PC is associated with progressive depletion of normal PC, B-cell precursors and CD34(+) HSC in the BM, also with a parallel increase in PB. In an ex vivo model, normal PC, B-cell precursors and CD34(+) HSC from MGUS and SMM, but not MM patients, were able to abrogate the migration of clonal PC into serial concentrations of SDF-1. Overall, our results show that progressive competition and replacement of normal BM cells by clonal PC is associated with more advanced disease in patients with MGUS, SMM and MM. Leukemia (2011) 25, 697-706; doi:10.1038/leu.2010.320; published online 21 January 2011