4.7 Review

Altered pathways and targeted therapy in double hit lymphoma

Journal

JOURNAL OF HEMATOLOGY & ONCOLOGY
Volume 15, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13045-022-01249-9

Keywords

Double hit lymphoma; Diffuse large B-cell lymphoma; Genetic alterations; Targeted therapy; Chemotherapy

Funding

  1. National Natural Science Foundation of China [81973172, 82003579]
  2. Natural Science Foundation of Zhejiang Province [LR21H300003, LQ21H300005]
  3. Science and Technology Program of Traditional Chinese Medicine, Zhejiang [2021ZB038]

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This article summarizes the genetic alterations in double hit lymphoma (DHL) and elucidates their implications on cellular processes, including apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. The ongoing and potential therapeutic strategies and targeted drugs based on these alterations are reviewed. Understanding DHL studies will provide insight into the disease and facilitate the discovery of more effective treatment strategies.
High-grade B-cell lymphoma with translocations involving MYC and BCL2 or BCL6, usually referred to as double hit lymphoma (DHL), is an aggressive hematological malignance with distinct genetic features and poor clinical prognosis. Current standard chemoimmunotherapy fails to confer satisfying outcomes and few targeted therapeutics are available for the treatment against DHL. Recently, the delineating of the genetic landscape in tumors has provided insight into both biology and targeted therapies. Therefore, it is essential to understand the altered signaling pathways of DHL to develop treatment strategies with better clinical benefits. Herein, we summarized the genetic alterations in the two DHL subtypes (DHL-BCL2 and DHL-BCL6). We further elucidate their implications on cellular processes, including anti-apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.

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