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Non-Hodgkin Lymphoma
An increase in MYC copy number has a progressive negative prognostic impact in patients with diffuse large B-cell and high-grade lymphoma, who may benefit from intensified treatment regimens
Ferrata Storti Foundation
Haematologica 2020 Volume 105(1):1369-1378
Francesca Schieppati,1* Piera Balzarini,2* Simona Fisogni,2 Alessandro Re,1 Chiara Pagani,1 Nicola Bianchetti,1 Lorenzo Micheli,2 Angela Passi,1 Samantha Ferrari,1 Adriana Maifredi, 1Chiara Bottelli,1 Rossella Leopaldo,1 Vilma Pellegrini,2 Fabio Facchetti,2 Giuseppe Rossi1 and Alessandra Tucci1
1Department of Hematology, ASST Spedali Civili di Brescia and 2Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy
*FS and PB contributed equally to this work.
ABSTRACT
MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncount- able number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respec- tively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correla- tion between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse progno- sis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be supe- rior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.
Introduction
Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heteroge- neous group of diseases.1 The survival of patients with DLBCL has significantly improved since rituximab (R) was added to cyclophosphamide, doxorubicin, vin- cristine and prednisone (CHOP) therapy, and R-CHOP has now become the stan- dard of care. The International Prognostic Index (IPI)2 and the Revised-International Prognostic Index (R-IPI)3 are useful tools to stratify patients in different risk classes. However, despite this, 30-40% of these patients are not cured by R-CHOP or R-CHOP-like regimens.4 In the last two decades, much effort has been made to identify patients at high risk of treatment failure, using morphological subtyping,5,6 identification of cell of origin by gene expression profiling,7 BCL2 and MYC protein expression by immunohistochemistry,8 and molecular insights by genetic stud- ies.9,10 In particular, different authors have demonstrated a negative prognostic impact of chromosomal aberration affecting the MYC gene locus in patients with
Correspondence:
FRANCESCA SCHIEPPATI
fschieppati@gmail.com
Received: April 6, 2019. Accepted: August 8, 2019. Pre-published: August 8, 2019.
doi:10.3324/haematol.2019.223891
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/5/1369
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