Role of BCL2 and MYC Alterations in Patients with Diffuse Large B-Cell Lymphoma
Authors: Bento Leyre , Martinez-Laperche Carolina , Noriega Víctor , Kwon Mi , Font Patricia , Osorio Santiago , Menárguez Javier , Buno Ismael , Diez Martin Jose Luis 
Published: October 2019

Abstract
Abstract 5218

INTRODUCTION:
Diffuse large B-cell lymphoma (DLBCL) represents more than 80% of high grade lymphomas and is considered a heterogeneous entity regarding clinical presentation, morphology, molecular and cytogenetic features. The Revised International Prognostic Index (R-IPI) is a clinically useful prognostic index that may help guide treatment. In this context, BCL2 and MYC gene rearrangements, that have been associated to specific variants of lymphoma, seem to have a prognostic implication. Consideration of these genetic markers together with classical parameters could contribute to a better stratification of patients.

OBJETIVE:
To analyze the incidence and possible clinical relevance of BCL2 and MYC gene alterations in the outcome of patients with DLBCL.

PATIENTS/METHODS:
This retrospective analysis included 20 patients with DLBCL (January 2008-April 2011), 74% (20/27) males with a median age of 70 years (range 17–82). Median follow-up was 300 days (range 17–1134). Fluorescence in situ hybridization (FISH) was performed on paraffin-embedded (n=12) or fresh (“touch-down” preparation) samples (n=8) from different tissues (7 lymphadenopathies, 3 central nervous system, 3 biologic fluids and 7 others). Each sample was hybridized with break-apart probes for BCL2 (18q21) and MYC (8q24) genes (Vysis Inc). 200 nuclei were scored per slide to reach 7% sensitivity.

RESULTS:
Seventy percent (14/20) of patients analyzed showed BCL2 and/or MYC alterations at diagnosis (rearrangement and/or extra signals). BCL2 was present as unique alteration in 30% (6/20) of the samples, MYC was present as unique alteration in 30% (6/20) and 10% (2/20) showed both BCL2 and MYC rearrangement (Table 1).
Two out of six patients with BCL2 as unique alteration showed rearragement, were treated with standard chemotherapy (R-CHOP or high dose of Citarabine/Methotrexate in central nervous system) and both patients relapsed. The other 4 patients presented extra signals as BCL2 alteration and also received standard chemotherapy. Fifty percent of these patients relapsed (Table 1).
On the other hand, 3 out of 6 patients with MYC as unique alteration presented gene rearrangement, they were treated with standard chemotherapy, and all 3 relapsed. The other 3 patients with MYC alterations presented extra signals, received standard chemotherapy and 33.3% (1/3) relapsed.
Finally, the 2 patients with simultaneous BCL2 and MYC rearrangement were treated with intensive chemotherapy and they reached and maintained complete remission.

CONCLUSIONS:
According to the results obtained from this study, FISH analysis on paraffin-embedded or fresh samples from lymphoma tissues is a feasible and useful technique at diagnosis in DLBCL patients. Although genetic markers are not included in the R-IPI score, the identification of BCL2 and/or MYC alterations at diagnosis, associated to other biological markers, could help to identify a subgroup of high risk patients who could benefit from more aggressive therapies. Further studies of larger series and genes are needed to confirm this observation.

Disclosures:
No relevant conflicts of interest to declare.