Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches

The present study will be divided into 5 phases:

1. Collection of bone marrow and peripheral blood (PB) samples from AML patients at diagnosis;
2. Measurement of Midregional Proadrenomedullin (MR-proADM) plasma concentrations with an Immunoluminometric Assay of newly diagnosed AML patients not affected by concomitant cardiovascular disease or sepsis.
3. Analysis of exosomes and microvesicles derived from PB and bone marrow samples of AML patients and culture media collected from AML samples stimulated with ADM and/or ADM (22-52)
4. Study of adrenomedullin system in leukemic stem cells (CD44+/CD38-/CD31+/Lin-) in order to define a correlated expression of ADM and ADM receptors (RAMPs, PAM) with adhesion molecules (CD31, CD38, CD44s, CD44v6), cell cycle regulatory proteins (p21, p27) and genes or molecules involved in the hematopoietic differentiation process (Cul5, CD11b, CD11c, CD66, CD14, CD15, PML-RARα)
5. In vitro evaluation of ADM activity in the growth, maturation and trans-endothelial migration of blasts and/or fusion of leukemic cells with endothelial cells. To do this, leukemic cells will be alternatively cultured by using in vitro models of endosteal and vascular niches.