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1、REVIEWERS COMMENTS PLUS REBUTTAL LETTERThis manuscript explores the in vivo models for leukemogenesis. It has many good features including comprehensive tabulation of the models currently published in the literature. It also deals with the use of ES cell mediated development for leukemia models effe
2、ctively before moving on to the equally important and valuable retroviral mediated gene transfer models that have been used to great effect in defining transforming properties of, for example, chromosome translocation products. The review has a scholarly nature, especially in the final two thirds. T
3、he abstract and introduction are more disappointing. The abstract needs to be completely rewritten with careful attention to detail. The sentence beginning furthermore is unfathomable. What does the compartment mean? The first phase of the introduction also disappoints. The authors need to think abo
4、ut what they are trying to say in these initial phases and set out the aims of the review more clearly. Sentences like the one beginning 8 lines up on page 7 need more thought. Similarly the 1st sentence of the 2nd paragraph on page 10. The use of transgenic as a noun needs to be considered as do wo
5、rds like inactuate. Equally sentences like that on page 15 line 3 need thought as to construction and precision. In this case control comparators need to be mentioned. The authors need to think more too about the target audience as non hematologists. Clear but concise explanation of detail in key ar
6、eas would help, like the use of the word compartment, see above. As stated previously the authors draw the right conclusions on where this field is at presently but there is work to do on the manuscript. One minor point is that theophyline is a cAMP phosphodiesterase inhibitorRe: MS#ONC-2007-00800AE
7、2 Review: Genetic Models of Acute Myeloid Leukaemia. Dear Editor, Sincerest thanks for your response and reviewers comments on our manuscript. We sincerely apologise for the great time it has taken us to respond to these comments (due to force majeaure with first author), and hope that a revised ver
8、sion of the manuscript will still be considered by Oncogene. We have modified the paper in response to the extensive and insightful reviewer comments. We have added additional explanations for non-haematologists and additional table (Table 1) to fully address the reviewers comments. Furthermore we h
9、ave rewritten sections of the manuscript and we hope that this comply with the referees remarks. We will respond to the comments point counter point. 1. This manuscript explores the in vivo models for leukemogenesis. It has many good features including comprehensive tabulation of the models currentl
10、y published in the literature. It also deals with the use of ES cell mediated development for leukemia models effectively before moving on to the equally important and valuable retroviral mediated gene transfer models that have been used to great effect in defining transforming properties of, for ex
11、ample, chromosome translocation products. The review has a scholarly nature, especially in the final two thirds. The abstract and introduction are more disappointing. The abstract needs to be completely rewritten with careful attention to detail. We have rewritten both the abstract and introduction
12、in line with the reviewers comments. We hope that these sections now give more focus to the scope of this review. 2. The sentence beginning furthermore is unfathomable. This sentence has been revised. 3. What does the compartment mean? The use of the word “compartment” has been completely revised an
13、d replaced throughout the manuscript with more precise definitions 4. The first phase of the introduction also disappoints. The authors need to think about what they are trying to say in these initial phases and set out the aims of the review more clearly. Please see point 1. 5. Sentences like the o
14、ne beginning 8 lines up on page 7 need more thought. Similarly the 1st sentence of the 2nd paragraph on page 10. Both these sentences have been rewritten, and we suggest that these revisions give greater clarity to the points being made. 6. The use of transgenic as a noun needs to be considered, as
15、do words like inactuate. We agree with the reviewers and have revised use of these words accordingly. 7. Equally sentences like that on page 15 line 3 need thought as to construction and precision. In this case control comparators need to be mentioned. In response to this comment we have reconstruct
16、ed the sentence and included relevant control comparators for mice treated with ENU. 8. The authors need to think more too about the target audience as non-hematologists. Clear but concise explanation of detail in key areas would help, like the use of the word compartment, see above. We have now inc
17、luded explanations of key terms and greater definition of human AML biology for non-haematologists throughout the text, particularly in the introduction and start of new sections where particular models are discussed e.g. APL models (page 6, last paragraph) AML/ETO (page 9, last paragraph) etc. or terms introduced e.g. MDS (page 11 line 1). Furthermore we have included a new table (Table 1), which outlines the clinical and biological characteristics of AML, for non- haematologists.
