Endothelial progenitor cells display clonal restriction in multiple myeloma.
Endothelial progenitor cells display clonal restriction in multiple myeloma.
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DOI：
10.1186/1471-2407-6-161
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发表时间：
2006-06-22
期刊：
影响因子：
3.8
通讯作者：
Batuman OA
中科院分区：
文献类型：
--
作者：
Braunstein M;Ozçelik T;Bağişlar S;Vakil V;Smith EL;Dai K;Akyerli CB;Batuman OA
在多发性骨髓瘤（MM）中，增加的新血管生成有助于肿瘤生长和疾病进展。内皮祖细胞（EPCs）水平的增加有助于MM中的新血管生成，重要的是，与疾病活动和治疗反应相关。为了了解负责增加EPC水平和MM中的新血管生成功能的机制，我们通过人类雄激素受体测定（HUMARA）确定女性患者的X染色体失活（XCI）模式来研究这些细胞是否是克隆的。此外，研究了EPC和骨髓细胞中是否存在克隆型免疫球蛋白重链（IGH）基因重排，这表明B细胞中存在克隆性;因此，其在EPC中的存在表明MM中的肿瘤细胞与提供肿瘤新血管形成的内皮细胞之间存在密切的遗传联系。共有23名未接受化疗的连续患者进行了研究。在18例患者中筛选发现11例在外周血单个核细胞中显示等位基因AR，并通过HUMARA进一步研究这些患者在EPCs和毛根细胞中的XCI模式。在2例通过HUMARA克隆EPCs的患者和另外5例新患者中，使用IGH可变基因（VH）家族特异性引物进行PCR，研究EPCs的IGH基因重排。在11例患者中，通过HUMARA对EPCs进行分析，发现64%（n = 7）的患者存在显著的偏斜（单个等位基因表达≥ 77%）。在其中4例患者中，XCI偏态极端（单个等位基因表达≥ 90%）。相反，毛根细胞的XCI是随机的。7例患者中，71%（n = 5）的EPCs和骨髓细胞扩增出相同的产物，而健康对照组EPCs中未发现IGH重排。此外，与EPCs随机XCI的患者不同，EPCs中XCI偏斜的患者，高龄与较差的临床状态相关。我们的研究结果表明，内皮祖细胞在至少一个实质性的MM患者亚群与肿瘤克隆，这是一个重要的机制，在MM肿瘤新生血管的上调。
In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH). In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI. Our results suggest that EPCs in at least a substantial subpopulation of MM patients are related to the neoplastic clone and that this is an important mechanism for upregulation of tumor neovascularization in MM.
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DOI：
10.1073/pnas.93.24.13931
发表时间：
1996-11-26
影响因子：
11.1
作者：
Bergsagel, PL;Chesi, M;Kuehl, WM
通讯作者：
Kuehl, WM
影响因子：
4
作者：
Kristiansen, M;Langerod, A;Orstavik, KH
通讯作者：
Orstavik, KH
影响因子：
6.5
作者：
Pruneri, G;Ponzoni, M;Viale, G
通讯作者：
Viale, G
影响因子：
11.2
作者：
Fonseca, Rafael;Barlogie, Bart;Avet-Loiseau, Herve
通讯作者：
Avet-Loiseau, Herve
影响因子：
6.5
作者：
Jacobson, JL;Hussein, MA;Crowley, JJ
通讯作者：
Crowley, JJ