All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
The authors have adequately addressed the issues raised by the referees.
[# PeerJ Staff Note - this decision was reviewed and approved by Paula Soares, a PeerJ Section Editor covering this Section #]
Please consider all points raised by the referees.
[# PeerJ Staff Note: Please ensure that all review comments are addressed in a response letter and any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate. It is a common mistake to address reviewer questions in the response letter but not in the revised manuscript. If a reviewer raised a question then your readers will probably have the same question so you should ensure that the manuscript can stand alone without the response letter. Directions on how to prepare a response letter can be found at: https://peerj.com/benefits/academic-rebuttal-letters/ #]
This is a well written paper dealing with an important issue in the field of acute myeloid leukemia diagnosis and treatment. I believe this paper is offering a relevant contribution to the knowledge of the disease. It is clear and not ambigous. Easy to be read and understood. I do not have major comments, just from the ending point of view:
Article meets the required targets. Rerences are more than suffient ( can be reduced). Too many figures.
Very well desuigned retrospective registry study
The paper is too long and can be significantly reduced without losing an important message.
This is a retrospective research article based on different data base screening and analysis. Because this is not a prospective research study conclusion must be more prudent limiting to suggest prospective controlled studies. Authors correctly underlined this limitation in the last discussion paragraphs but I believe limitation should be reported in the abstracts also. Moreover I suggest a more prudent title.
Too many figures.
.
I support pubblication after editing revision
no comment
As a computational analysis study, this manuscript directly goes to the single CXCL12 gene without giving a systematic overview of differential genes or cytokines in AML, so there is weakness in experimental design before diving into this particular cytokine.
no comment.
This study explored the prognostic value of CXCL12 in acute myeloid leukemia by associating CXCL12 expression with immune infiltration, pathway enrichment, and cancer survival. The exploration is generally valuable analysis, however, there are multiple concerns as following.
- The decision to focus on specifically CXCL12 is not clear. The authors can improve by at least starting looking at genes/cytokines most differential between AML and control to provide the reason to focus on this specific cytokine, rather than cherry-picking one cytokine.
- The authors used CIBERSORT for immune deconvolution; due to the high heterogeneity of immune infiltration deconvolution algorithms with different cell types available, a better practice is to utilize multiple deconvolution methods to cross-check the association with immune infiltrates. For example, popular deconvolution methods include TIMER, CIBERSORT, quanTIseq, xCell, MCP-counter, EPIC, and immuneDeconv. These methods can be used to validate whether the significant B cell difference is reproducible for CXCL12 expression. In fact, the CIBERSORT algorithm is incorrectly written as CIBERSOFT in line 130.
- The unit of gene expression from GTEx and any transformation shall be noted, e.g. in Fig1a whether this is TPM or log scale. Same issue in Fig1b for CCLE expression unit, and also for all following figures.
- In comparison with the hematopoietic stem cells of differentiated states, there shall be statistics and number of samples shown to prove the higher expression of CXCL12 in HSC than the differentiated states.
- Given that CXCL12 in the current manuscript likely link to monocytes and some other immune cells, it is suggested that single-cell data can be used to show the cell-type resource of CXCL12, and study the potential interaction with other cell types based on cytokine-receptor interaction.
- There are analyses of mutation status with possible synergy with CXCL12. There shall be mechanistic research into why the different mutations can be related to the CXCL12 level.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.