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Review
. 2022 Mar 22:12:829983.
doi: 10.3389/fonc.2022.829983. eCollection 2022.

Biology and Treatment of Richter Transformation

Adalgisa Condoluci  1   2   3 , Davide Rossi  1   2   3
Affiliations
Review

Biology and Treatment of Richter Transformation

Adalgisa Condoluci et al. Front Oncol. .

Abstract

Richter transformation (RT), defined as the development of an aggressive lymphoma on a background of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), represents a clinical unmet need because of its dismal prognosis. An increasing body of knowledge in the field of RT is arising from the recent development of preclinical models depicting the biology underlying this aggressive disease. Consistently, new therapeutic strategies based on a genetic rationale are exploring actionable pathogenic pathways to improve the outcome of patients in this setting. In this review, we summarize the current understandings on RT biology and the available treatment options.

Keywords: CLL; DLBCL; Hodgkin lymphoma; Richter syndrome; Richter transformation; biology; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Richter transformation: intrinsic vulnerabilities and targets for treatment. A representation of the molecular pathogenesis of Richter transformation, resulting from a number of epigenetic and genetic lesions occurring in the tumor cell population. Recurrently mutated genes affect DNA repair, B cell receptor, and chromatine modification. Created with BioRender.com.
Figure 2
Figure 2
Microenvironmental crosstalks and druggable targets in Richter transformation. Pathway activation and changes in immune checkpoints profile are also involved in transformation. Communication between the tumoral cells, dendritic cells, tumor associated macrophages (TAM), and T cells is established by direct contact, chemokine/cytokine receptors, adhesion molecules and ligand-receptor interactions. Immune inhibitory molecules (PD-L1 among others) facilitate tumor cells to evade immune-response and maintain tolerance. All of the here represented are druggable targets in RT. BCR, B cell receptor; DC, dendritic cells; TAM, tumor associate macrophage. Created with BioRender.com.
Figure 3
Figure 3
Proposed algorithm for the management of suspected diffuse large B-cell Richter transformation (DLBCL-RT). aCLL, accelerated chronic lymphocytic leukemia; auto-SCT, autologous stem cell transplantation; DLBCL, diffuse large B-cell lymphoma; NA, novel agents; RIC allo-SCT, reduced intensity conditioning stem cell transplantation. Created with BioRender.com.
See this image and copyright information in PMC

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