What is it about?

We found that Mixed-Lineage Kinase Domain-Like (MLKL) expression is associated with Overall Survival of Glioma patients. In contrast with what was previously shown for other tumors, the higher its expression, the worse the survival rate. As MLKL is effector molecule of necroptosis, a pro-inflammatory cell death pathway, we hypothesize that the resulting increased inflammatory reaction may be in part responsible for the observed worst prognosis.

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Why is it important?

Currently, Glioma diagnosis mostly relies on two molecular markers, namely IDH mutation and 1p/19q codeletion tests to subgroup patients into Oligodendrogliomas, Astrocitomas or Glioblastomas. However, those markers still fail to underscore critical differences in the clinical outcomes of some of these patients. Our work showed that patients can be categorized into high or low MLKL expression groups with clinically distinct outcomes independently of the diagnostic classification and age. Contrary to what was seen to other non-glial tumors, patients with high MLKL expression showed and average of ~68% increased risk of death compared with their low expression counterparts, with the same diagnostic and age.

Perspectives

We are actively pursuing collaborative opportunities to close the divide between our clinical breakthroughs and their real-world application. By harnessing larger cohorts, our goal is to explore a more practical translational method for integrating this classification approach into the everyday clinical practices of Adult Glioma Management, for exemple utilizing either IHC or qPCR.

Ricardo Weinlich
Hospital Israelita Albert Einstein

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This page is a summary of: Higher Mixed lineage Kinase Domain-like protein (MLKL) is associated with worst overall survival in adult-type diffuse glioma patients, PLoS ONE, August 2023, PLOS,
DOI: 10.1371/journal.pone.0291019.
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