Etude du Microenvironnement médullaire Dans Les Leucémies Aiguës de l'Enfant
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University Hospital, Tours
- Enrollment
- 40
- Locations
- 6
- Primary Endpoint
- Oxygen Consumption Rate
Study Overview
Brief Summary
Acute leukemia (AL) is the most common cancer in children. Despite the optimization of chemotherapy treatments and the development of supportive care, a certain number of LAs relapse and/or progress to death of the child. It therefore seems essential to try to better understand the physiopathology and the mechanisms of resistance to treatment of these diseases.
Detailed Description
Acute leukemia (AL) is the most common cancer in children. Despite the optimization of chemotherapy treatments and the development of supportive care, a certain number of AL's relapse and/or progress to death of the child. It therefore seems essential to try to better understand the physiopathology and the mechanisms of resistance to treatment of these diseases. The study of the microenvironment appears in this context as a promising avenue. The bone marrow microenvironment is composed of an extracellular matrix and cells, in particular mesenchymal stromal stem cells (MSC's). In adult acute leukemia, it has been clearly demonstrated that these microenvironment cells are reprogrammed by leukemia cells to allow the development and proliferation of the latter. Links have also been demonstrated in acute leukemia between the cells of the microenvironment and resistance to chemotherapy. In a certain number of cases, the support of the microenvironment for the development of leukemia or resistance to chemotherapy involves modulation of the energy metabolism of leukemia cells. This notably involves interactions between leukemic cells and MSCs and re-programming of the energy metabolism of the latter. To date, there are only very few studies concerning the role of the microenvironment in acute childhood leukemia and none to date has specifically studied the energy metabolism (oxidative phosphorylation and glycolysis) of MSCs.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 15 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •for patients with AL:
- •Child with acute lymphoblastic or myeloblastic leukemia at diagnosis
- •Not having received prior hematological treatment
- •Aged 1 to 15 years old
- •Whose 2 parents, or the holder of parental authority, have signed a consent enlightened.
- •Affiliated patient or beneficiary of a social security scheme.
- •Control group patients:
- •Child undergoing orthopedic surgery exposing the bone marrow (osteotomy of the pelvis).
- •Aged between 1 and 15 years old.
- •Having no pathology of hematological origin.
- •Not having received any treatment that could interfere with the functioning of the bone marrow.
- •Whose 2 parents or the holder of parental authority have signed a consent enlightened.
- •Affiliated patient or beneficiary of a social security scheme.
Exclusion Criteria
- •for patients with AL:
- •Patient under 1 year old and over 15 years old.
- •Contraindication to myelogram.
- •Absence of signature of the informed consent by the 2 parents or the holder of parental authority.
- •Patients with relapsed acute lymphoblastic or myeloblastic leukemia.
- •Having received prior hematological treatments.
- •Parents with physical or mental condition not allowing to understand the informed consent.
- •Control group patients
- •Patient under 1 year old and over 15 years old.
- •Having an underlying haematological pathology.
- •Absence of signature of the informed consent by the 2 parents or the holder of parental authority.
- •Having received prior hematological treatments.
- •Parents with physical or mental condition not allowing to understand informed consent.
Outcomes
Primary Outcomes
Oxygen Consumption Rate
Time Frame: At inclusion
Difference in oxidative phosphorylation measured by OCR (Oxygen Consumption Rate) in pmol/min/nd DNA between the mesenchymal stromal stem cells (MSCs) of children with Acute Leukemia and those of children without blood diseases.
Secondary Outcomes
- Difference in Extra Cellular Acidification Rate(At inclusion)
- Difference in Reactive Oxygen Species(At inclusion)
- Differences in transcriptomic signatures between MSCs and MSC subpopulations(At inclusion)
- Difference in doubling time in culture(At inclusion)
- Difference in Immunophenotypic profile(At inclusion)
- Differences in cytokine profiles within the bone marrow(At inclusion)
- Difference in mutational profiles between MSCs and leukemia cells(At inclusion)