T-cell acute lymphoblastic leukemia progression is supported by inflammatory molecules including Hepatocyte Growth factor

Abstract

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disorder characterized by an increased proliferation of immature T lymphocytes precursors. T-ALL treatment includes chemotherapy with strong side effects, and patients that undergo relapse display poor prognosis. Although cell-intrinsic oncogenic pathways are well-studied, the tumor microenvironment, like inflammatory cellular and molecular components is less explored in T-ALL. We sought to determine the composition of the inflammatory microenvironment induced by T-ALL, and its role in T-ALL progression. Methods: Two mouse T-ALL cell models were injected into immunocompetent mice. We used anti-Ly6G, and clodronate liposomes to suppress neutrophils and phagocytes, respectively. 5-(N-ethylcarboxamido)adenosine (NECA), an agonist of adenosine receptors was used to decrease inflammatory molecules secretion. Findings: We show that T-ALLs enhance blood neutrophils and resident monocytes, accompanied with a plasmatic acute secretion of inflammatory molecules. Depleting neutrophils or resident monocytes does not modulate plasmatic inflammatory molecule secretion and mice survival. However, inhibiting the secretion of inflammatory molecules by microenvironment with NECA diminishes T-ALL progression enhancing mouse survival. We uncovered Hepatocyte Growth Factor (HGF), T-ALL-driven and the most decreased molecule with NECA, as a potential therapeutic target in T-ALL. Interpretation: Altogether, we identified a signature of inflammatory molecules that can potentially be involved in T-ALL evolution and uncovered HGF as a new potential therapeutic target.