Page 133 - Haematologica-April 2018

Global mRNA changes in stroma-bound lymphoma cells
Among 116 overlapping genes, a core gene set of 13 genes (fold change >2-fold) was identified. The core gene set contains genes that relate to the four functional themes and that have previously been coupled to lymphoma pathogenesis (CCL3, CCL4, ICAM1, NFKB1 and IL21R) as well as DUSP4, ETV5, IL15RA, IL4I1 and NFKBIE that have been described in a lymphoma context. The pres- ence of the NFKBIE NF-κB inhibitor may appear contra- dictory, but the apoptotic/anti-apoptotic responses to the NF-κB pathway activity have been shown to be pluralistic and context dependent.50 The set also includes three genes which have not previously been associated with lym- phoma pathology, MFSD2A, SEMA7A and TMEM2, sug- gesting the existence of at least some relevant genes that remain to be characterized.
In summary, this first genome-wide, systematic study shows that genes differentially expressed in stromal cell adherent MCL cells are predominantly involved in anti- apoptosis, B-cell signaling, cell adhesion and early mitosis.
Overlaps with clinical MCL and CLL data sets suggest that the identified genes also play important roles within can- cer microenvironments in patients. The results support the utility of this in vitro model system for dissecting microen- vironmental signaling and identify a list of 13 critical genes that should be a focus for future studies.
Acknowledgments
We would like to thank the core facility at Novum, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska hospital.
Funding
The study was supported by grants from: The Swedish Research Council (to AW), The Swedish Cancer Society (to AW and BS), The Cancer Society in Stockholm (to BS), The Stockholm County Council (to BS) and Karolinska Institutet (to AW and BS).
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