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Non-Hodgkin Lymphoma
MYC rearrangement but not extra MYC copies is an independent prognostic factor in patients with mantle cell lymphoma
Ferrata Storti Foundation
Haematologica 2021 Volume 106(5):1381-1389
Lifu Wang,1,2 Guilin Tang,1 L. Jeffrey Medeiros,1 Jie Xu,1 Wenting Huang,1,3 C. Cameron Yin,1 Michael Wang,4 Preetesh Jain,4 Pei Lin1 and Shaoying Li1
1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Pathology, Henan Provincial People’s Hospital, Zhengzhou, Henan, China; 3Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China and 4Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
ABSTRACT
Mantle cell lymphoma (MCL) with MYC rearrangement (MYC-R) is rare and little is known about the importance of MYC extra copies (EC) in the absence of MYC-R in MCL patients. This study includes 88 MCL patients with MYC tested by fluorescence in situ hybridization and/or conventional cytogenetics, including 27 with MYC-R, 21 with MYC-EC, and 40 with normal MYC-NL. MCL patients with MYC-R more often had blastoid/pleomorphic morphology; a higher fre- quency of CD10, MYC, and simultaneous MYC and BCL2 expression; a higher level of MYC; and a higher Ki67 proliferation rate (P<0.05) than those without MYC-R. Although patients with MYC-R more frequently received intensive chemotherapy (P=0.001), their overall survival (OS) was significantly shorter than those without MYC-R. Compared with patients with MYC/BCL2 double-hit lymphoma (DHL), patients with MYC-R MCL had a similar OS but more commonly had bone marrow involvement, Ann Arbor stage IV disease, and a different immunophenotype. MCL patients with MYC-EC showed an OS intermediate between those with MYC-R and MYC-NL, either all or only blastoid/pleomorphic MCL patients includ- ed. Multivariate analysis showed that MYC-R, but not MYC-EC, had an independent and negative impact on OS. In conclusion, MYC-R but not MYC-EC showed a higher MYC expression and is an adverse prognostic factor for MCL patients. Although the OS of MCL patients with MYC-R is similar to that of MYC/BCL2 DHL patients, these groups have different clin- icopathologic features supporting the retention of MCL with MYC-R in the category of MCL, as recommended in the revised World Health Organization classification.
Introduction
Mantle cell lymphoma (MCL) is an aggressive, incurable B-cell lymphoma char- acterized by t(11;14)(q13;q32) that juxtaposes the CCND1 gene adjacent to IGH on the derivative chromosome 14. This translocation results in constitutive overex- pression of cyclin D1 and deregulation of the cell cycle at the G1/S phase transi- tion.1-3 Data from mouse models and clinical studies suggest that CCND1 is a weak oncogene and that secondary genetic aberrations likely contribute to MCL devel- opment.4,5 Furthermore, conventional cytogenetic studies have shown that the t(11;14) is rarely an isolated genetic abnormality in MCL. The lymphoma cells dis- play a high degree of genomic instability and tend to accumulate additional chro- mosomal and molecular alterations, which likely lead to clinical progression of dis- ease.1,6,7
MYC is one of the most frequently deregulated oncogenes in human malignan- cies.8,9 t(8;14)(q24;q32)/MYC-IGH was the first recurrent translocation identified in lymphomas, initially in Burkitt lymphoma (BL). Subsequently, it was learned that
Correspondence:
SHAOYING LI
sli6@mdanderson.org
Received: November 13, 2019. Accepted: March 27, 2020. Pre-published: April 9, 2020.
https://doi.org/10.3324/haematol.2019.243071
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