Comparative analysis of systemic and tumor microenvironment proteomes of children with b-cell acute lymphocytic leukemia at diagnosis and after induction treatment.

ABSTRACT: Among the childhood diseases, B-cell acute lymphocytic leukemia (B-ALL) is the most frequent type of cancer. In spite of recent advances concerning disease treatment, cytotoxic chemotherapy remains as the first line of treatment in several countries, and the modifications induced by such drugs in the organism remains poorly understood. In this context, the present study provided a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-LLA treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. 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). 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-LLA 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. 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.

INSTRUMENT(S): Synapt HDMS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Blood Plasma, Bone Marrow

DISEASE(S): Childhood Acute Lymphocytic Leukemia

SUBMITTER: Eliana Abdelhay  

LAB HEAD: Carolina Panis

PROVIDER: PXD021584 | Pride | 2020-12-14

REPOSITORIES: Pride