Hodgkin lymphoma cell lines: to separate the wheat from the chaff

Abstract

Characteristic components of Hodgkin lymphoma (HL) tissue are the mono- or multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Given the challenges of isolating these rare malignant cells and the difficulty in culturing cells from patients, many investigators have tried to establish cell lines in efforts to develop cellular tools for in vitro studies. A limited number of HL cell lines exist and have provided valuable insights into HL pathobiology. A literature survey indicated that 35 cell lines derived from HL patients have been published. To determine whether all these alleged HL cell lines hold up to scrutiny, we examined the available data and also put some of these cell lines to the test of hierarchical clustering, providing additional information regarding assignment to cell line type and tissue derivation. Hierarchical clustering separated the bona fide (classical) HL cell lines completely from cell lines derived from other lymphoma categories and proved conclusively that HL cell lines represent a distinct entity, irrespective of the cellular origin of the HRS cells. We conclude by pointing out the need for an intensified search for new cell culture avenues in order to develop a new generation of informative HL cell lines covering more widely the spectrum of HL stages and subtypes.

NKL homeobox gene NKX2-2 is aberrantly expressed in Hodgkin lymphoma

“…While most available HL cell lines belong to the cHL group DEV represents the NLPHL entity [5, 6]. This discrimination is also supported by recent cluster analyses using expression profiling data from all bona fide HL cell lines [7].…”

The LL-100 Cell Lines Panel: Tool for Molecular Leukemia–Lymphoma Research

“…Recent years have truly seen a welcome expansion of the scientific knowledge potential of LL cell lines [4]. Panels of specific LL cell line subtypes have also been extensively characterized [5][6][7][8] and presented as models for addressing unique topics, for example, to explore therapeutic innovations and to illuminate mechanisms of chromatin and transcriptional regulation in tumor cells [9].…”

“…In a literature survey of some 554 published LL cell lines, we found that 54% were established from patients at relapse or at a refractory/terminal disease stage, while 34% were derived from patient samples at diagnosis or at initial presentation [ 11 ]. Among the available ten bona fide Hodgkin lymphoma cell lines, 10/10 were derived from patients in terminal/refractory stages, 7/10 from pleural effusions (a sign of advanced disease), and 8/10 from nodular sclerosis-subtype Hodgkin lymphoma (at the expense of the three other histological subtypes) [ 7 ]. Hence, with regard to the successful establishment of new cell lines—at least in Hodgkin lymphoma—there is clearly a strong bias towards putatively more aggressive primary cells with specific and possibly more mutations.…”

Molecular Pathogenesis of Hodgkin Lymphoma: Past, Present, Future

“…The development of monoclonal antibodies by Kohler and Milstein in 1975 led to the identification of CD30 positivity in H- and RS-cells [ 8 , 9 , 10 ]. Giant leaps in our understanding were made possible by the establishment and characterization of the first, L-428 [ 11 , 12 ], and subsequent Hodgkin cell lines [ 13 ]. Polymerase chain reaction (PCR) techniques combined with single-cell micro-dissection allowed to molecularly analyze the mononuclear H-cells and bi- or multinuclear RS-cells from diagnostic lymph node biopsies [ 14 ].…”