PONE-D-24-51496Pretreatment expression of miR-191a may predict response to the induction chemotherapy based on cytarabine in acute myeloid leukemia patients – a single-center studyPLOS ONE

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this paper, the Authors report on the impact of pre-treatment expression of miRNA -191 on response rate in AML patients. They found that miRNA-191 positively correlated with achievement of CR and the presence of miRNA-191 was higher among FLT3-ITD negative patients. Conversely, FLT3-ITD was related to a reduced probability of CR.

The role of miRNAs in AML is still not completely elucidated and new informations are needed.

However, at the current stage, the paper has major issues that hamper pubblication.

Major

The cohort is small and heterogenous, patient receiving intensive anthracycline + citarabine induction are included alongside patients who received less intensive therapy without antracyclines. This may introduce a bias. Furhtermore, it is stated that 44 patients were enrolled but data on treatment received is reported in 31 (23 + 3 +5) patients only. Also, response rate are reported only for those 31 patients (22/31 achieved CR and 9/31 did not respond).

The Authors adopted the old ELN 2010 classification that included 4 risk group. I think that a newer edition (either 2017 or, better, 2022) should be adopted.

It is unclear how the variable for the predictive model were selected.

miRNA-191 is less frequent among FLT3-ITD negative patients and FLT3-ITD was related to a lower chance of CR (quite unusually, as this mutation usually does not impact CR rate in intensively treated patients but increased relapse risk). Can the Author try different predictive models without the inclusion of miRNA-191 or with other combination of variables in order to be certain that the effect is not mostly due to the presence or absence of FLT3-ITD.

Confidence intervals in the predictive model are quite wide and cross the unity (0.98-89.5 and 0.593 - 108.16 for miRNA-191 and FLT3-ITD, respectively). This is likely due to the small patient cohort.

The information would have been significantly more relevant if MRD data were provided

- the Author decided to omit survival analysis. I think it could have been useful.

Minor

there are several typos throughout the manuscript (e.g. NMP1 instead of NPM1).

Reviewer #2: Dear authors

The introduction is dense with information, which can make it difficult for readers to follow.

Some sentences are lengthy and contain multiple ideas, which may confuse readers.

Some information is repeated or could be consolidated.

The statistics provided regarding the incidence of AML could be presented more clearly. For example, stating the incidence rates in a comparative format would enhance clarity.

While the section states that patient characteristics are presented in Table 1, it does not provide any summary or highlights of these characteristics in the text.

The methodology for RNA isolation and analysis is described, but it lacks details about the quality control measures taken (e.g., RNA quality assessment) and how the specificity of the miRNA assays was ensured.

The statistical analysis section mentions using nonparametric tests due to the lack of normal distribution but does not provide any justification for the choice of tests used.

There is no justification provided for the sample size of 44 patients. A brief explanation of how this sample size was determined (e.g., power analysis) would strengthen the study’s methodology.

While the section states that patient characteristics are presented in Table 1, it does not provide any summary or highlights of these characteristics in the text.

There is little acknowledgment of potential methodological limitations within the study.

The discussion lacks a detailed description of the statistical methods used to analyze the correlations mentioned.

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Reviewer #1: Yes:  Fabio Guolo

Reviewer #2: No

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Attachment

Submitted filename: Review 1 microRNA PLOS ONE.docx

<p>Pretreatment expression of miR-191a may predict response to the induction chemotherapy based on cytarabine in acute myeloid leukemia patients – a single-center study

PONE-D-24-51496R1

Dear Dr. Szymczyk,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Francesco Bertolini, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: Yes:  Fabio Guolo

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