The Role of Epigenetic Modifier Mutations in Peripheral T-Cell Lymphomas
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsIn the current manuscript, the authors comprehensively summarize the role of epigenetic modifier mutations in peripheral T-cell lymphomas (PTCL). The manuscript is written well, and the information will be very helpful for the readers to understand PTCL biology. Only some minor comments that would improve an already very nice manuscript.
1. A recent manuscript (Blood, 2022;140(11):1278-1290: PMID: 35639959) has clearly demonstrated the role of DNMT3A mutation in PTCL-NOS from clinical and molecular aspects. This may be worth mentioning in the manuscript.
2. Also, a recent paper (Sci Transl Med. 2023;15(714):eadi7244: PMID: 37729434) has revealed that TP63-fusions, which are identified in a small portion of PTCL, can cause epigenetic changes toward lymphoma genesis. This paper may be worth mentioning in the manuscript.
Author Response
In the current manuscript, the authors comprehensively summarize the role of epigenetic modifier mutations in peripheral T-cell lymphomas (PTCL). The manuscript is written well, and the information will be very helpful for the readers to understand PTCL biology. Only some minor comments that would improve an already very nice manuscript.
Answer: Thank you for your remarks. After adding the suggested references, we detected other two sources that were mentioned in text at subchapter 2.4. only with PMIDs, now they are added with EndNote to the reference list.
- A recent manuscript (Blood, 2022;140(11):1278-1290: PMID: 35639959) has clearly demonstrated the role of DNMT3A mutation in PTCL-NOS from clinical and molecular aspects. This may be worth mentioning in the manuscript.
Answer: Thank you for this suggestion. Indeed, the manuscript published by Herek et al, is very important for the topic and significantly increases the quality of this manuscript. We added this reference at subchapter 2.3.
- Also, a recent paper (Sci Transl Med. 2023;15(714):eadi7244: PMID: 37729434) has revealed that TP63-fusions, which are identified in a small portion of PTCL, can cause epigenetic changes toward lymphoma genesis. This paper may be worth mentioning in the manuscript.
Answer: Thank you for your valuable comment. Indeed, this paper is important and we added the information related to TP63 fusion and how these fusions can increase therapy vulnerability in the case of EZH2 inhibitors. Please find the correction in the text.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe reviewed article elucidates the role of specific genetic modifications in the context of the pathogenesis and treatment of peripheral T-cell lymphomas. In my opinion, the publication is interesting and inspiring for further research in the described topic. However, I believe that the paper contains relatively little epidemiological and clinical data. It primarily focuses on the molecular basis. If possible, I would suggest providing a more detailed presentation of the described epigenetic changes within the mentioned scope. Please also clarify the abbreviations in the abstract, such as PTCL-NOS, TFH, and AITL. PTCL-NOS and AITL should also be further characterized in the Introduction of the paper. The text of the paper also includes some phrases unnecessarily capitalized, such as "or Histone acetylation" or "Decitabine (D)."
Comments on the Quality of English LanguageMinor editing of English language required.
Author Response
The reviewed article elucidates the role of specific genetic modifications in the context of the pathogenesis and treatment of peripheral T-cell lymphomas. In my opinion, the publication is interesting and inspiring for further research in the described topic.
However, I believe that the paper contains relatively little epidemiological and clinical data. It primarily focuses on the molecular basis.
If possible, I would suggest providing a more detailed presentation of the described epigenetic changes within the mentioned scope.
Answer: Thank you for your suggestions. We added into the text details regarding the presence of mutations in specific genes that encode proteins involved in methylation, focusing on the therapeutical perspective of these mutations that may lead to personalized therapeutical approaches. All changes are marked with track changes.
Please also clarify the abbreviations in the abstract, such as PTCL-NOS, TFH, and AITL.
Answer: Thank you for this observation. Indeed, the abbreviation is not clarified in the abstract. We added all the details, please find the corrections in the abstract.
PTCL-NOS and AITL should also be further characterized in the Introduction of the paper.
Answer: thank you for your remarks. We added information regarding PTCLs in the introduction chapter discussing the clinical characteristics and risk factors for each subtype of PTCLs. Please find all the changes in the text, with track changes.
The text of the paper also includes some phrases unnecessarily capitalized, such as "or Histone acetylation" or "Decitabine (D)."
Answer: We checked for these capitalized words and we changed it according to your remarks. Thank you for your critical review which has significantly improved our work. We hope that we managed to answer all your remarks and to the other two reviewers and make the manuscript suitable for being published.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe focus of the article is to review the role of epigenetic modifiers in PTCL.
The major concern with this article is that the authors spend too much time explaining how methylation works, its history and the various genes that play a role in the process of methylation. The authors fail to connect how methylation plays a role in PTCL which is the entire objective of this study.
It's my opinion that the authors need to focus more on the specific genes that are methylated in PTCL. Any studies that are conducted to study the effects of targeting methylation in PTCL. If not, this study is just a chapter on history, process and importance of methylation in oncology.
Author Response
The major concern with this article is that the authors spend too much time explaining how methylation works, its history and the various genes that play a role in the process of methylation. The authors fail to connect how methylation plays a role in PTCL which is the entire objective of this study.
It's my opinion that the authors need to focus more on the specific genes that are methylated in PTCL. Any studies that are conducted to study the effects of targeting methylation in PTCL. If not, this study is just a chapter on history, process and importance of methylation in oncology.
Answer: Thank you for your critical review of our manuscript. Indeed, we focused very much on methylation and how it works, aiming to introduce the readers to the process of methylation and to explain in detail how it works and why is so important in epigenetics.
After receiving the three revisions, from you and other two reviewers we changed the manuscript by adding valuable information to the introduction part and we did our best to explain in chapter two the connection between the methylation and PTCL and how methylation process is involved in PTCL evolution and development, moreover we tried to highlight how demethylation agents can improve the clinical outcomes in the case of PTCL.
Please find our correction in the main text, highlighted with track changes. Changes were made in the introduction part, in chapter 2 and in subchapter 2.4., depending on which methylator was evaluated.
We tried to highlight the importance of methylation in PTCL, the role of methylators and how mutations can lead to poor outcome, moreover we hope that by adding this information it is visible that the methylation landscape is crucial when choosing a therapy and the hypomethylating agents can be useful in treating PTCLs.
We appreciate your effort to review this work and we believe that your remarks helped us to increase the quality of this manuscript.
Round 2
Reviewer 3 Report
Comments and Suggestions for AuthorsI have no more comments for the authors.
