Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status: Enrolling

Conditions: Acute Myeloid Leukemia

Treatments: Other: Adrenomedullin

Study type: Interventional

Funder types: Other

Identifiers

NCT04460963

AML2220

Details and patient eligibility

About

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.

Enrollment: 72 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with new diagnosis of primary or secondary AML.
2. Participant is willing and able to give signed written informed consent according to ICH/EU/GCP and national local laws.
3. Male or Female, aged >18 years.

Exclusion criteria

1. Patients affected by concomitant cardiovascular disease , such as essential hypertension (any grade), chronic renal failure (creatinine>1.5 mg/dL), heart failure (any NYHA class), and peripheral arterial occlusive diseases, or sepsis.
2. Patients affected by HIV, B or C hepatitis.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 1 patient group

Biological evaluation

Other group

Description:

Adrenomedullin evaluation at diagnosis at first CR and 1 year of follow-up

Treatment:

Other: Adrenomedullin