Increased MYC copy number is an independent prognostic factor in patients with diffuse large B-cell lymphoma

Abstract

Patients with double-hit or triple-hit lymphoma have a significantly worse prognosis compared to patients with diffuse large B-cell lymphoma without MYC rearrangement. However, the prognostic importance of extra copies of MYC, BCL2, or BCL6 has not been fully explored. We studied 663 patients with de novo diffuse large B-cell lymphoma in whom the status of MYC/8q24, BCL2/18q21, and BCL6/3q27 were assessed by fluorescence in situ hybridization. Cases of double or triple extra copy lymphoma were defined by the presence of increased MYC copies and increased BCL2 and/or BCL6 copies or rearrangement. In total, 76 patients with diffuse large B-cell lymphoma had MYC extra copies including 43 cases of double or triple extra copy lymphoma; 105 patients had diffuse large B-cell lymphoma with MYC-R including 56 double- or triple-hit lymphoma; and 482 diffuse large B-cell lymphoma patients had no MYC abnormality (MYC normal). Patients with MYC extra copies, similar to MYC-R, had a worse overall survival compared with MYC normal patients (both P<0.01). The prognosis between patients with MYC extra copies and MYC-R was not statistically significantly different (P=0.086). Cell-of-origin classification failed to correlate with survival in the MYC extra copies group, similar to the MYC-R patient group. Compared with patients with double- or triple-hit lymphoma, patients with double or triple extra copy lymphoma had a higher complete remission rate (P=0.02), but there was no significant statistical difference in overall survival (P=0.089). Intensive induction chemotherapy regimens improved the overall survival of patients with double or triple extra copy lymphoma, but there was no significant improvement of overall survival in patients with MYC-R tumors. Multivariate analysis showed that MYC extra copy in diffuse large B-cell lymphoma is an independent poor prognostic factor, similar to MYC rearrangement.

MYC rearrangement and MYC/BCL2 double expression but not cell‐of‐origin predict prognosis in R‐CHOP treated diffuse large B‐cell lymphoma

“…Translocations involving MYC are a hallmark of Burkitt lymphoma, but they can occur in 5%‐15% of DLBCL, conferring a poorer prognosis in DLBCL patients treated with R‐CHOP and CHOP‐like regimens . In multivariate Cox regression modeling, MYC rearrangement was predictive of inferior survival and provided prognostic information independent of IPI score or stage for both OS and EFS . In a recent report from the Lunenburg Lymphoma Biomarker Consortium, MYC ‐R was associated with a significantly shorter PFS and OS, with a strong time‐dependent effect within the first 24 months after diagnosis; interestingly, the adverse prognostic impact of MYC ‐R in that study was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner.…”

“…5,23,[25][26][27][28][29][30][31] In multivariate Cox regression modeling, MYC rearrangement was predictive of inferior survival and provided prognostic information independent of IPI score or stage for both OS and EFS. 26,32 In a recent report from the Lunenburg Lymphoma Biomarker Consortium, 33 with t(14;18) had a significantly worse survival compared with those without the translocation. 37 A recent study showed that isolated BCL2 translocation was not predictive of outcome in the DLBCL patients as a whole, but did predict outcome in those with GCB type: Therefore, MYC/BCL2 DE is much more common than DHL.…”

Genetic alterations in B cell lymphoma subtypes as potential biomarkers for non-invasive diagnosis, prognosis, therapy, and disease monitoring

“…MYC overexpression due to genetic aberrancies (e.g., translocation and amplification) can be used as a prognostic biomarker for certain B cell NHL subtypes. Based on a recent report, MYC amplifications or rearrangements can independently predict overall survival in patients of DLBCL (Quesada et al, 2017). Application of next-generation sequencing (NGS)-based technologies such as whole exome sequencing revealed the genomic mutational landscape of different types of B cell lymphomas.…”

Comprehensive histopathological diagnostics of aggressive B-cell lymphomas based on the updated criteria of the World Health Organisation’s 2017 classification

“…Unique genetic changes, especially mutations such as GNA13 and EZH2 in GCB and MYD88, CARD11, and CD79B in ABC are found, respectively [6,7]. Chromosomal translocations in DLBCL involving regions with BCL6 (3q27), BCL2 [t(14;18) (q32;q21.3)], and MYC (single hit) comprise, respectively, approximately 30% (with predominance in ABC subtype), 20-30% (more commonly in GCB subtype), and 8-14% (similar distribution among ABC and GCB subtype) [8,9,10,11,12,13,14,15,16,17,18]. It is estimated that approximately 50% of DLBCL with MYC translocation demonstrate BCL2 and/or BCL6 rearrangement and that cases should be transferred to the high-grade B-cell lymphoma category [1,19,20].…”