Potential role of hypoxia in early stages of Hodgkin lymphoma pathogenesis

15Citations
Citations of this article
26Readers
Mendeley users who have this article in their library.

Abstract

A unique feature of the germinal center B cell-derived Hodgkin and Reed/Sternberg cells of classical Hodgkin lymphoma is their lost B cell phenotype and the aberrant expression of factors of other hematopoietic cell types, including ID2 and NOTCH1. As cellular dedifferentiation and upregulation of ID2 and NOTCH1 are typical consequences of a hypoxic response, we wondered whether hypoxia may impose an HRS cell-like phenotype in B cells. Culturing normal B cells or cell lines of germinal center-type diffuse large B-cell lymphoma under hypoxic conditions caused partial downregulation of several B cell markers, ID2 upregulation, and increased NOTCH1 activity. The hypoxic cells acquired further features of Hodgkin and Reed/Sternberg cells, including increased JUN expression, and enhanced NFkB activity. The Hodgkin and Reed/Sternberg cell-expressed epigenetic regulators KDM4C and PCGF2, as well as the phosphatase DUSP1 were partially induced in hypoxic B cells. Inhibition of DUSP1 was toxic for classical Hodgkin lymphoma cell lines. Thus, hypoxia induces key Hodgkin and Reed/Sternberg cell characteristics in mature B cells. We speculate that hypoxic conditions in the germinal center may impose phenotypic changes in germinal center B cells, promoting their survival and initiating their differentiation towards a Hodgkin and Reed/Sternberg cell-like phenotype. These may then be stabilized by transforming events in the Hodgkin and Reed/Sternberg precursor cells.

Cite

CITATION STYLE

APA

Wein, F., Otto, T., Lambertz, P., Fandrey, J., Hansmann, M. L., & Küppers, R. (2015). Potential role of hypoxia in early stages of Hodgkin lymphoma pathogenesis. Haematologica, 100(10), 1320–1326. https://doi.org/10.3324/haematol.2015.127498

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free