Sherif Marwa, Schäfer Hendrik, Scharf Sonja, van Oostendorp Vivienne, Sadeghi Shoreh Deli Aresu, Loth Andreas G, Piel Matthieu, Hansmann Martin-Leo, Oellerich Thomas, Fend Falko, Quintanilla-Martinez Leticia, Hartmann Sylvia
Dr. Senckenberg Institute of Pathology, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
Department of Otolaryngology, Head and Neck Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany.
Br J Haematol. 2024 Dec;205(6):2327-2337. doi: 10.1111/bjh.19778. Epub 2024 Oct 2.
Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent aggressive B-cell lymphoma. The group is heterogeneous and the outcome is variable. A variety of approaches have been employed with the objective of improving the stratification of DLBCL patients according to their prognosis, based on the cell of origin. Recently, distinct genetic subtypes of DLBCL have been identified. Given the importance of cell migration in immune cells, the objective of this study was to ascertain whether different genetic subtypes of DLBCL exhibit disparate migration abilities. MCD- and EZB-type DLBCL cell lines were subjected to testing to ascertain their basal velocity in straight microchannels and their ability to overcome tight constrictions of 2 μm. The EZB-type cell lines showed superior basal migration velocity and constriction passage time, and a similar trend was observed in live cell imaging of native human DLBCL tissue. In addition, MCD-type DLBCL exhibited significantly elevated levels of nuclear lamin A/C, which is responsible for the stiffness of the nuclear envelope and could thus explain the disparate migration behaviours observed among these subtypes. Our study suggests that different genetic subtypes of DLBCL may not only influence the outcome after therapy but also the motility of the tumour cells.
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的侵袭性B细胞淋巴瘤。该组具有异质性，预后也各不相同。为了根据起源细胞改善DLBCL患者的预后分层，人们采用了多种方法。最近，已鉴定出DLBCL的不同基因亚型。鉴于细胞迁移在免疫细胞中的重要性，本研究的目的是确定DLBCL的不同基因亚型是否表现出不同的迁移能力。对MCD型和EZB型DLBCL细胞系进行测试，以确定它们在直微通道中的基础速度以及克服2μm紧密收缩的能力。EZB型细胞系表现出更高的基础迁移速度和收缩通过时间，在天然人类DLBCL组织的活细胞成像中也观察到了类似趋势。此外，MCD型DLBCL的核纤层蛋白A/C水平显著升高，核纤层蛋白A/C负责核膜的硬度，因此可以解释这些亚型之间观察到的不同迁移行为。我们的研究表明，DLBCL的不同基因亚型不仅可能影响治疗后的结果，还可能影响肿瘤细胞的运动性。
