Aim: To perform a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-cell acute lymphocytic leukemia (B-ALL) treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. Methods: to reach this goal, PB and BM plasma samples were comparatively analyzed by using label-free proteomics at two endpoints: at diagnosis (D0) and the end of the cumulative induction phase treatment (D28). Results: the resulting differentially expressed proteins were explored by bioinformatics approaches aiming to identify the main gene ontology processes, pathways and transcription factors altered by chemotherapy, as well to understand B-ALL biology in each compartment at D0. At D0, PB was characterized as a pro-inflammatory environment, with the involvement of several downregulated coagulation proteins as KNG, plasmin and plasminogen. D28 was characterized predominantly by immune response-related processes, and the super expression of the transcription factor IRF3 and transthyretin. RUNX1 was pointed out as a common transcription factor found in both D0 and D28. Discussion: In the present study, the comparative analysis of the proteomic profile between the systemic (blood) and tumor (bone marrow) microenvironments provided a picture regarding the main proteins and processes that are present at diagnosis(D0), and triggered by the induction chemotherapy (D28) in the blood from ALL-B patients. The comparison performed between D0 and D28 allowed to describe the cumulative effect of cytotoxic treatment, understand the main processes present in ALL-B at diagnosis, and to know the main proteins differentially expressed that are relevant in each compartment before and after chemotherapy. Conclusion: considering that most of these proteins were not described in B-ALL literature, these findings added to understanding disease biology at diagnosis, and highlighted some important proteins and processes that may contribute to our understanding about the mechanisms concerning the impact of chemotherapy in disease resolution. Keywords: B-acute lymphocytic leukemia; Chemotherapy; Proteomics; Induction phase.