Double hit and double expressors in lymphoma: Definition and treatment

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Aggressive B-cell lymphomas present challenges in curability due to emerging biologic subsets and prognostic markers.
• Concurrent MYC and BCL2 deregulation, identified at genomic or protein levels, is a key area of investigation in diffuse large B-cell lymphomas (DLBCL).

Purpose of the Study:

• To highlight the significance of identifying concurrent MYC and BCL2 deregulation in aggressive B-cell lymphomas.
• To discuss the implications of double-hit lymphoma (DHL) and double-expressor lymphoma (DEL) in DLBCL patient outcomes.
• To address practical considerations in the identification, prognosis, and management of DHL and DEL.

Main Methods:

• Review of current literature on MYC and BCL2 deregulation in aggressive B-cell lymphomas.
• Analysis of diagnostic criteria for double-hit lymphoma (DHL) and double-expressor lymphoma (DEL).
• Discussion of prognostic implications and management strategies for DHL and DEL.

Main Results:

• Double-hit lymphoma (DHL), characterized by dual gene rearrangements (MYC and BCL2/BCL6), accounts for 5-7% of DLBCL cases with rare long-term survivors.
• Double-expressor lymphoma (DEL), defined by MYC and BCL2 protein overexpression without genomic rearrangements, comprises 20-30% of DLBCL cases and is associated with poor outcomes.
• Concurrent MYC and BCL2 deregulation significantly impacts DLBCL curability.

Conclusions:

• Identification of MYC and BCL2 deregulation is critical for understanding and managing aggressive B-cell lymphomas.
• DHL and DEL represent important subsets of DLBCL with distinct molecular features and poor prognoses.
• Further research and clinical strategies are needed to improve outcomes for patients with DHL and DEL.