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慢性粒细胞白血病静止期和增殖期干细胞/祖细胞之间的生物物理差异。

Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells.

作者信息

Guz Nataliia V, Patel Sapan J, Dokukin Maxim E, Clarkson Bayard, Sokolov Igor

机构信息

Department of Chemistry, Clarkson University, Potsdam, NY, USA.

Department of Chemistry, Clarkson University, Potsdam, NY, USA; Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, Molecular Pharmacology and Chemistry Program, New York, NY.

出版信息

Nanomedicine. 2016 Nov;12(8):2429-2437. doi: 10.1016/j.nano.2016.06.016. Epub 2016 Jul 16.

Abstract

The treatment of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder has improved recently, but most patients have not yet been cured. Some patients develop resistance to the available tyrosine kinase treatments. Persistence of residual quiescent CML stem cells (LSCs) that later resume proliferation is another common cause of recurrence or relapse of CML. Eradication of quiescent LSCs is a promising approach to prevent recurrence of CML. Here we report on new biophysical differences between quiescent and proliferating CD34+ LSCs, and speculate how this information could be of use to eradicate quiescent LSCs. Using AFM measurements on cells collected from four untreated CML patients, substantial differences are observed between quiescent and proliferating cells in the elastic modulus, pericellular brush length and its grafting density at the single cell level. The higher pericellular brush densities of quiescent LSCs are common for all samples. The significance of these observations is discussed.

摘要

慢性髓性白血病(CML)是一种克隆性骨髓增殖性疾病,其治疗方法最近有所改进,但大多数患者尚未治愈。一些患者对现有的酪氨酸激酶治疗产生耐药性。残留的静止CML干细胞(LSCs)持续存在,随后恢复增殖,这是CML复发或再发的另一个常见原因。根除静止LSCs是预防CML复发的一种有前景的方法。在此,我们报告了静止和增殖的CD34 + LSCs之间新的生物物理差异,并推测这些信息如何有助于根除静止LSCs。通过对从四名未经治疗的CML患者收集的细胞进行原子力显微镜(AFM)测量,在单细胞水平上观察到静止细胞和增殖细胞在弹性模量、细胞周刷长度及其嫁接密度方面存在显著差异。静止LSCs较高的细胞周刷密度在所有样本中都很常见。我们讨论了这些观察结果的意义。

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