Re-envisioning risk biomarkers in acute myeloid leukemia (AML) at single-cell level

Introduction

Acute myeloid leukemia (AML) is one of the most aggressive, clinically and biologically heterogeneous hematological malignancies. The different genetics classify disease entities and define the prognostic risk category to which AML patients are assigned and the treatment choices.

Genetic Classification

There is one entity, the AML with nucleophosmin (NPM1) gene mutations, that accounts for one-third of all adult AML (the most frequent). Another gene mutation, the Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD), acts as the tipping point for patient risk definition. This drastically worsens the prognosis and affects treatment in those 40% of patients where it is detected.

Research Background

This has been a main field of research for Prof. Maria Paola Martelli and her team for years, specifically through her ERC consolidator grant ContraNPM1AML. Here, she will exploit concepts stemming from her ERC-funded studies on the key role of kinases in the NPM1-mutated AML development, response to therapy, and initiating relapse.

Focus on Prognosis

The focus will be on the 60% of patients regarded as having a favorable prognosis, who nevertheless in 40% of cases will relapse with an extremely dismal outcome. Currently, successful strategies to identify novel frontline key markers to refine risk are not available.

Project Overview

reMARK-AML takes on the challenge of changing prognostic risk parameters, aiming to re-envision the marker at the single-cell level. A first strategy has been designed and will be tested for proof-of-concept in patients through a prospective non-interventional study.

Collaboration and Development

We have established contacts with industrial partners for the development of fit-for-purpose diagnostic assay prototypes to be tested in the study.

Future Challenges

The success of reMARK-AML will open the next challenge of developing marketable diagnostic kits and defining a strong business plan in order to measure the impact of our idea and proof-of-concept in the real-world clinical setting.