A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma.
A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma.
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DOI：
10.1111/bjh.13927
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发表时间：
2016-04
影响因子：
6.5
通讯作者：
Azab AK
中科院分区：
文献类型：
--
作者：
Muz B;de la Puente P;Azab F;Luderer MJ;King J;Vij R;Azab AK
数十年来，CD 138（也称为SDC 1）一直是检测多发性骨髓瘤（MM）细胞的金标准表面标志物;然而，耐药残留和循环MM细胞显示该标志物的表达较低。在这项研究中，我们已经表明硼替佐米治疗后残留的MM细胞是缺氧的。这种药物暴露和缺氧的组合下调其CD 138的表达，从而使该标志物不适合检测残留或其他缺氧MM细胞，如循环肿瘤细胞，在MM。因此，我们开发了一种替代的生物标志物集，检测骨髓瘤细胞独立于他们的缺氧和CD 138表达状态在体外，体内和原发性MM患者。新的标志物能够将克隆性CD 138阴性人群识别为MM患者骨髓和外周血中的微小残留病。需要进一步研究以描述该人群作为MM预后标志物的作用。
CD138 (also termed SDC1) has been the gold-standard surface marker to detect multiple myeloma (MM) cells for decades; however, drug-resistant residual and circulating MM cells were shown to have lower expression of this marker. In this study, we have shown that residual MM cells following bortezomib treatment are hypoxic. This combination of drug exposure and hypoxia down-regulates their CD138 expression, thereby making this marker unsuitable for detecting residual or other hypoxic MM cells, such as circulating tumour cells, in MM. Hence, we developed an alternative biomarker set which detects myeloma cells independent of their hypoxic and CD138 expression status in vitro, in vivo and in primary MM patients. The new markers were able to identify a clonal CD138-negative population as minimal residual disease in the bone marrow and peripheral blood of MM patients. Further investigation to characterize the role of this population as a prognostic marker in MM is warranted.