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Impact of MYC increased copy number in DLBCL
    impact on the efficacy of less intensive treatments to be evaluated. In any case, the treatment choice was based on the individual clinician’s decision.
Overall, no differences emerged between standard chemo-immunotherapy and more aggressive regimens both in CR achievement and in survival, particularly in the subgroup of patients with a limited number of MYC abnormalities (≤4). On the other hand, the survival of patients with MYC-T, MYC-ICN >4 and MYC-AMP seemed to be superior if intensive treatments were used, and DA-EPOCH among intensive treatments seemed to be the most effective for patients with MYC-T and MYC- AMP. Nevertheless, these retrospective data should be interpreted with caution, particularly in the absence of sta- tistical significance; further studies are need in larger groups of patients and these results confirmed in prospec- tive studies.
The present study further confirms that the occurrence of a BCL-2 translocation has a negative prognostic influence. In contrast to the presence of MYC extra-copies, the pres- ence of extra-copies of BCL-2 and BCL-6 genes did not
carry any adverse prognostic significance. Likewise, BCL-2 and BCL-6 extra-copies did not worsen the outcome of patients with MYC-ICN in the study by Quesada et al.27
In conclusion, our study shows that, in DLBCL patients, MYC extra-copies are more frequently detected by FISH studies than MYC translocations, highlighting the impor- tance of FISH testing at diagnosis of DLBCL. While having 3-4 copies of MYC correlated with a high rate of treat- ment response and a good prognosis also with standard immuno-chemotherapy, lymphoma showing >4 copies of MYC had a more aggressive disease, comparable to MYC-translocated DLBCL, and may be more responsive to intensified treatment approaches. Further investigation is warranted to clarify the biological implications of numerical aberrations of MYC and the possible benefit of specific or intensified therapeutic strategies.
Acknowledgments
The authors would like to thank all doctors and nurses who provided patients’ care at the Department of Hematology, ASST Spedali Civili di Brescia.
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