Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma
, Nuria Z. Veglio 2, Henning Nilius 3, Barbara Jeker 2, Ulrike Bacher 4 and Thomas Pabst 2,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript entitled Rising Prevalence of Low Frequency PPM1D Gene Mutations after second HDCT in Multiple Myeloma by Seipel et al. is a well-written study that provides interesting and meaningful results showing the presence of PPM1D gene mutations in PB of MM patients undergoing ASCT. The authors showed inferior survival in patients with PPM1D mutation compared with PPM1D wild type. I have a few comments/suggestions:
1. What’s the biological function of PPM1D gene mutation in myeloma? Does PPM1D gene mutation leads to gene function suppression, activation, or gain of other functions? It’s suggested to include this background information either in the Introduction or Discussion.
2. Does PPM1D mutation correlate with del(17p) and other chromosomal abnormalities in myeloma?
3. In correlates with previous question, is PPM1D mutation an independent prognostic factors for myeloma patients?
4. In figure 1, the number of patients in each group should be provided in the figures or the figure legends.
Author Response
Cimb-3104530 Reviewer 1.
The manuscript entitled Rising Prevalence of Low Frequency PPM1D Gene Mutations after second HDCT in Multiple Myeloma by Seipel et al. is a well-written study that provides interesting and meaningful results showing the presence of PPM1D gene mutations in PB of MM patients undergoing ASCT. The authors showed inferior survival in patients with PPM1D mutation compared with PPM1D wild type. I have a few comments/suggestions:
Response: We thank the reviewer for the positive evaluation and the helpful comments. We added more information in the introduction and results section and added a multivariate analysis of the data. We believe that the manuscript has been substantially improved.
- What’s the biological function of PPM1D gene mutation in myeloma? Does PPM1D gene mutation leads to gene function suppression, activation, or gain of other functions? It’s suggested to include this background information either in the Introduction or Discussion.
Response: PPM1D gene alterations are typically nonsense or frameshift mutations in exon 6, resulting in truncated protein products promoting cell proliferation [13][14]. The truncated PPM1D protein variants are able to dephosphorylate p53, but are not recognized by the APC/C complex, leading to stabilization and accumulation of a constitutively active protein phosphatase. We have added this information on PPM1D gene mutations and PPM1D protein function in the introduction, lane 61.
- Does PPM1D mutation correlate with del(17p) and other chromosomal abnormalities in myeloma?
Response: The PPM1D gene is located on chromosome 17q, but the presence of PPM1D gene mutations was not associated to deletion of chromosome 17p. There was, however, an elevated prevalence of cytogenetic aberration +1q in the PPM1Dmut subset. We have added this information to the results section, lane 186.
- In correlates with previous question, is PPM1D mutation an independent prognostic factors for myeloma patients?
Response: The independent nature of a given prognostic factor may be established by multivariate statistical analysis delineating its independence from other prognostic factors. Data in tables 1 and 2 were analyzed by univariate analysis. We have added a multivariate analysis in new table 3. Our data suggest that PPM1D gene mutation may be a predictor of inferior survival in myeloma patients treated with HDCT/ASCT independent of age, ISS and cytogenetic risk.
- In figure 1, the number of patients in each group should be provided in the figures or the figure legends.
Response: We have added the number of patients in each group in the figures.
Submission Date
28 June 2024
Date of this review
08 Jul 2024 01:49:23
Date of revision: 22 July 2024
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript has almost 35% plagiarism. It's not suitable to accept for publication in such a form.
Comments on the Quality of English LanguageLanguage needs correction throughout the manuscript.
Author Response
Cimb-3104530 Reviewer 2.
The manuscript has almost 35% plagiarism. It's not suitable to accept for publication in such a form.
Language needs correction throughout the manuscript.
Submission Date
28 June 2024
Date of this review
12 Jul 2024 22:12:42
Response: The current paper on low frequency PPM1D gene mutations in multiple myeloma may have similarities with our previous paper on low frequency PPM1D gene mutations in diffuse large B-cell lymphoma (Seipel et al., Curr. Oncol. 2023, doi.org/10.3390/curroncol 30120762) as it is based on the same technology (NGS), focused on the same gene (PPM1D), with similarities in the introduction, methods and discussion section, but in a different hematological entity treated with different therapies. To avoid plagiarism all sentences from other sources have been referenced.
Date of revision: 22 July 2024
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsEven though it's your second paper on the same topic, it's not recommended to copy and paste the same sentences. The best practice is to rephrase the sentences or make significant changes to avoid plagiarism. I recommend you all go through the paper once again and try to minimize repetition as much as possible.
Author Response
Cimb-3104530 Review Round 2.
Even though it's your second paper on the same topic, it's not recommended to copy and paste the same sentences. The best practice is to rephrase the sentences or make significant changes to avoid plagiarism. I recommend you all go through the paper once again and try to minimize repetition as much as possible.
Date of this review
24 Jul 2024 22:29:24
Response: We scanned the entire manuscript on the free online plagiarismdetector.net and rephrased the detected sentences until all text was declared unique.
Date of revision: 26 July 2024
Author Response File: Author Response.docx
