Acute Myeloid Leukemia (AML) arises from the somatic acquisition of genetic alterations in hematopoietic progenitor or stem cells.
One of the main hallmarks of AML is heterogeneity in terms of morphology, immunophenotype, cytogenetics, and molecular abnormalities, this heterogeneity leads to an important clinical heterogeneity in term of response to chemotherapy and prognosis. , The European Leukemia Net recognizes three different prognostic risk group (favorable, intermediate and high). Patients with favorable or intermediate risk AML, theoretically, should be cured with pharmacological treatment only (chemo and in some cases targeted therapies). However, more of the 50% of patients with favorable or intermediate risk AML experience relapse. This heterogeneity in outcome is not only explained by genetics and it's probably due to the persistence of chemo-resistant leukemic stem cell (LSC) clone, and to its interaction with the bone marrow (BM) microenvironment.
This research project is focused on the analysis of the mesenchymal stem cells (MSCs) of the BM in order to deepen their connections with the LSC and their correlation with different genetic AML subgroups, and to evaluate their contribution to the outcome of favorable risk AML with Nucleophosmin 1 (NPM1) gene mutation.