PURPOSE: MYC rearrangement (MYC-R) occurs in approximately 10% of diffuse large B-cell lymphomas (DLBCLs) and has been associated with poor prognosis in many studies. The impact of MYC-R on prognosis may be influenced by the MYC partner gene (immunoglobulin [IG] or a non-IG gene). We evaluated a large cohort of patients through the Lunenburg Lymphoma Biomarker Consortium to validate the prognostic significance of MYC-R (single-, double-, and triple-hit status) in DLBCL within the context of the MYC partner gene. METHODS: The study cohort included patients with histologically confirmed DLBCL morphology derived from large prospective trials and patient registries in Europe and North America who were uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or the like. Fluorescence in situ hybridization for the MYC, BCL2, BCL6, and IG heavy and light chain loci was used, and results were correlated with clinical outcomes. RESULTS: A total of 5,117 patients were identified of whom 2,383 (47%) had biopsy material available to assess for MYC-R. MYC-R was present in 264 (11%) of 2,383 patients and was associated with a significantly shorter progression-free and overall survival, with a strong time-dependent effect within the first 24 months after diagnosis. The adverse prognostic impact of MYC-R was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner (hazard ratio, 2.4; 95% CI, 1.6 to 3.6; P < .001). CONCLUSION: The negative prognostic impact of MYC-R in DLBCL is largely observed in patients with MYC double hit/triple-hit disease in which MYC is translocated to an IG partner, and this effect is restricted to the first 2 years after diagnosis. Our results suggest that diagnostic strategies should be adopted to identify this high-risk cohort, and risk-adjusted therapeutic approaches should be refined further.
PURPOSE:MYC rearrangement (MYC-R) occurs in approximately 10% of diffuse large B-cell lymphomas (DLBCLs) and has been associated with poor prognosis in many studies. The impact of MYC-R on prognosis may be influenced by the MYC partner gene (immunoglobulin [IG] or a non-IG gene). We evaluated a large cohort of patients through the Lunenburg Lymphoma Biomarker Consortium to validate the prognostic significance of MYC-R (single-, double-, and triple-hit status) in DLBCL within the context of the MYC partner gene. METHODS: The study cohort included patients with histologically confirmed DLBCL morphology derived from large prospective trials and patient registries in Europe and North America who were uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or the like. Fluorescence in situ hybridization for the MYC, BCL2, BCL6, and IG heavy and light chain loci was used, and results were correlated with clinical outcomes. RESULTS: A total of 5,117 patients were identified of whom 2,383 (47%) had biopsy material available to assess for MYC-R. MYC-R was present in 264 (11%) of 2,383 patients and was associated with a significantly shorter progression-free and overall survival, with a strong time-dependent effect within the first 24 months after diagnosis. The adverse prognostic impact of MYC-R was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner (hazard ratio, 2.4; 95% CI, 1.6 to 3.6; P < .001). CONCLUSION: The negative prognostic impact of MYC-R in DLBCL is largely observed in patients with MYC double hit/triple-hit disease in which MYC is translocated to an IG partner, and this effect is restricted to the first 2 years after diagnosis. Our results suggest that diagnostic strategies should be adopted to identify this high-risk cohort, and risk-adjusted therapeutic approaches should be refined further.
Authors: Da Jung Kim; Taeyun Kim; Jee-Yeong Jeong; Jae-Cheol Jo; Won Sik Lee; Ho-Jin Shin; Ji Hyun Lee; Ho Sup Lee Journal: Int J Hematol Date: 2020-01-06 Impact factor: 2.490
Authors: Pallawi Torka; Shalin K Kothari; Suchitra Sundaram; Shaoying Li; L Jeffrey Medeiros; Emily C Ayers; Daniel J Landsburg; David A Bond; Kami J Maddocks; Anshu Giri; Brian Hess; Luu Q Pham; Ranjana Advani; Yang Liu; Stefan Klaus Barta; Julie M Vose; Michael C Churnetski; Jonathon B Cohen; Madelyn Burkart; Reem Karmali; Joanna Zurko; Amitkumar Mehta; Adam J Olszewski; Sarah Lee; Brian T Hill; Timothy F Burns; Frederick Lansigan; Emma Rabinovich; David Peace; Adrienne Groman; Kristopher Attwood; Francisco J Hernandez-Ilizaliturri Journal: Blood Adv Date: 2020-01-28
Authors: Mark Pieterse; Joost Swennenhuis; G Tjitske Los-de Vries; Amin Allahyar; Mehmet Yilmaz; Roos Leguit; Ruud W J Meijers; Robert van der Geize; Joost Vermaat; Arjen Cleven; Tom van Wezel; Arjan Diepstra; Léon C van Kempen; Nathalie J Hijmering; Phylicia Stathi; Milan Sharma; Adrien S J Melquiond; Paula J P de Vree; Marjon J A M Verstegen; Peter H L Krijger; Karima Hajo; Marieke Simonis; Agata Rakszewska; Max van Min; Daphne de Jong; Bauke Ylstra; Harma Feitsma; Erik Splinter; Wouter de Laat Journal: Nat Commun Date: 2021-06-07 Impact factor: 14.919