Profiles of Growth Factors Secreted by In Vitro-Stimulated Paediatric Acute Leukaemia Blasts of Myeloid and Lymphoid Origin

TL;DR

This study explores how different types of childhood leukemia cells release growth factors under various stimulations, revealing patterns that could help develop targeted treatments.

Contribution

This is the first study to comprehensively assess growth factor secretion by pediatric leukemia cells using a multiplex immunoassay.

Findings

AML blasts showed the highest basal secretion of G-CSF, GM-CSF, and VEGF.

PMA + I stimulation was the strongest inducer of growth factor release, especially in BCP-ALL and T-ALL blasts.

T-ALL blasts showed higher responsiveness to PHA and LPS stimulation compared to other leukemia types.

Abstract

The research on cytokine or growth factor (GF) release by leukaemic blasts is a largely unexplored area. This study aimed to evaluate the differential secretory potential of paediatric B-cell precursor and T-cell acute lymphoblastic leukaemia (BCP-ALL and T-ALL, respectively) and acute myeloid leukaemia cells (AMLs) for selected GFs, both basally and upon stimulation with phytohemagglutinin (PHA), lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate with ionophore A23187 (PMA + I). The concentrations of five GFs: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in the supernatants were measured using the Bio-Plex multiplex immunoassay. AML blasts showed the highest basal concentrations of G-CSF, GM-CSF, and VEGF. PHA and LPS stimulation non-selectively enhanced the secretion of G-CSF, GM-CSF, VEGF, and PDGF in BCP-ALL and AML blasts. PMA + I was the strongest GF release inducer, particularly for BCP-ALL and T-ALL blasts, with the latter also showing higher responsiveness to PHA and LPS. Our findings reveal differential, leukaemia-type dependent GF secretion patterns. Lineage-specific responses may be exploitable for targeted therapeutic approaches for distinct AL types. This study is the first to comprehensively assess the extracellular secretion of multiple GFs by paediatric AL cells in cultures using a Bio-Plex multiplex immunoassay.

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