CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients
CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients
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DOI：
10.1038/leu.2012.80
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发表时间：
2012-09-01
期刊：
影响因子：
11.4
通讯作者：
Sugiyama, H.
中科院分区：
文献类型：
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作者：
Hosen, N.;Matsuoka, Y.;Sugiyama, H.
据报道，克隆性多发性骨髓瘤（MM）细胞缺乏浆细胞标志物CD 138的表达。CD 19（+）克隆型B细胞在某些患者中可作为MM祖细胞。然而，目前尚不清楚CD 138阴性克隆源性MM浆细胞是否与克隆型CD 19（+）B细胞相同。我们发现，在体外MM集落形成细胞富集在CD 138（-）CD 19（-）CD 38（+）（+）浆细胞中，而CD 19（+）B细胞在本研究中检查的16个样本中从未形成MM集落。我们接下来使用SCID-rab模型，其能够在体内植入人MM。9例中有3例移植了CD 138（-）CD 19（-）CD 38（+）（+）浆细胞，但未检测到CD 19（+）B细胞的移植。在9例中的4例中，CD 138（+）浆细胞增殖MM，尽管比CD 138（-）细胞慢。最后，我们将13例MM患者的CD 19（+）B细胞移植到NOD/SCID IL 2 R γ c（-/-）小鼠中，但MM没有发生。这些结果表明，至少在某些MM患者中，CD 138阴性的克隆形成细胞是浆细胞而不是B细胞，并且包括CD 138（-）和CD 138（+）细胞在内的MM浆细胞具有在缺乏CD 19（+）B细胞的情况下在体内增殖MM克隆的潜力。
Clonogenic multiple myeloma (MM) cells reportedly lacked expression of plasma cell marker CD138. It was also shown that CD19(+) clonotypic B cells can serve as MM progenitor cells in some patients. However, it is unclear whether CD138-negative clonogenic MM plasma cells are identical to clonotypic CD19(+) B cells. We found that in vitro MM colony-forming cells were enriched in CD138(-) CD19(-) CD38(+) (+) plasma cells, while CD19(+) B cells never formed MM colonies in 16 samples examined in this study. We next used the SCID-rab model, which enables engraftment of human MM in vivo. CD138(-) CD19(-) CD38(+) (+) plasma cells engrafted in this model rapidly propagated MM in 3 out of 9 cases, while no engraftment of CD19(+) B cells was detected. In 4 out of 9 cases, CD138(+) plasma cells propagated MM, although more slowly than CD138(-) cells. Finally, we transplanted CD19(+) B cells from 13MM patients into NOD/SCID IL2R gamma c(-/-) mice, but MM did not develop. These results suggest that at least in some MM patients CD138-negative clonogenic cells are plasma cells rather than B cells, and that MM plasma cells including CD138(-) and CD138(+) cells have the potential to propagate MM clones in vivo in the absence of CD19(+) B cells.