Defining the Basal and Immunomodulatory Mediator-Induced Phosphoprotein Signature in Pediatric B Cell Acute Lymphoblastic Leukemia (B-ALL) Diagnostic Samples

Defining the Basal and Immunomodulatory Mediator-Induced Phosphoprotein Signature in Pediatric B Cell Acute Lymphoblastic Leukemia (B-ALL) Diagnostic Samples

It is theorized that dysregulated immune responses to infectious insults contribute to the development of pediatric B-ALL. In this context, our understanding of the immunomodulatory-mediator-induced signaling responses of leukemic blasts in pediatric B-ALL diagnostic samples is rather limited. Hence...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 24; no. 18; p. 13937
Main Authors: Khanolkar, Aaruni, Liu, Guorong, Simpson Schneider, Bridget M
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-09-2023
MDPI
Subjects:
Analysis
B cells
Chemokines
Cytokines
Hypotheses
Immune response
Immune system
immunomodulatory mediators
Inflammation
Leukemia
Lymphocytes
Mortality
pediatric B cell acute lymphoblastic leukemia (B-ALL)
Pediatrics
Phosphorylation
signal transducer and activator of transcription (STAT)
signaling
T cells
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Summary:It is theorized that dysregulated immune responses to infectious insults contribute to the development of pediatric B-ALL. In this context, our understanding of the immunomodulatory-mediator-induced signaling responses of leukemic blasts in pediatric B-ALL diagnostic samples is rather limited. Hence, in this study, we defined the signaling landscape of leukemic blasts, as well as normal mature B cells and T cells residing in diagnostic samples from 63 pediatric B-ALL patients. These samples were interrogated with a range of immunomodulatory-mediators within 24 h of collection, and phosflow analyses of downstream proximal signaling nodes were performed. Our data reveal evidence of basal hyperphosphorylation across a broad swath of these signaling nodes in leukemic blasts in contrast to normal mature B cells and T cells in the same sample. We also detected similarities in the phosphoprotein signature between blasts and mature B cells in response to IFNγ and IL-2 treatment, but significant divergence in the phosphoprotein signature was observed between blasts and mature B cells in response to IL-4, IL-7, IL-10, IL-21 and CD40 ligand treatment. Our results demonstrate the existence of both symmetry and asymmetry in the phosphoprotein signature between leukemic and non-leukemic cells in pediatric B-ALL diagnostic samples.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241813937