Harnessing proteomic vulnerabilities of disease biology to drive tailored treatment of leukemia

Although much progress has been made in the treatment of some types of acute leukemia, others are still associated with dismal prognosis in both children and adults. New therapeutic options that are tailored to the biology of the disease are urgently needed.

A promising avenue to exploit therapeutically is the interdependence of the leukemic cells and their local microenvironment (niche).

However, little is known about the molecular mechanisms involved in the interactions between leukemic cells and their niche during the phases of disease.

In particular, it is essential to study the proteins that ultimately represent the true effectors of disease.This project aims to advance the understanding of the proteomic interplay between leukemic cells and their direct environment across fetal, infant and adult life. We will apply a multitude of advanced proteomic technologies to primary acute leukemia cells and their niche.

These molecular analyses will be combined with functional assessments of perturbation of the leukemia-promoting protein networks that will establish therapeutic efficacy.

In a second part of the project, we will identify leukemia- and ontogeny-specific peptide antigens of the leukemic cells that exhibit crosstalk with the immune cells in the niche.

Through perturbation of leukemia-altered and ontogeny-specific proteins that we have identified in our previous work, we will assess the possibility to induce targetable leukemia-specific immunopeptides.