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NCT Number: NCT05792007

Study of the Medullary Microenvironment in Acute Childhood Leukemia

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.

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Key information

Age range

1 year–15 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service d'hématologie biologique-CHRU TOURS, Tours, France

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Biological sampling in patients

Procedure

blood and bone marrow samples from patients with Acute Leulemia.

Biological sampling in control patients

Procedure

blood and bone marrow samples from children undergoing orthopedic surgery exposing the bone marrow.(osteotomy of the pelvis).

Primary outcomes

  1. 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

  1. Difference in Extra Cellular Acidification Rate

    Time frame: At inclusion

    Difference in glycolysis, measured by the ECAR (Extra Cellular Acification Rate) in mpH/min/ng DNA between the MSCs of children with AL and those of children without hematological disease.

  2. Difference in Reactive Oxygen Species

    Time frame: At inclusion

    Difference in oxidative metabolism thanks to the measurement of reactive oxygen species (ROS), measured in MIF/isotype, between MSCs of children with AL and those of children without hematological disease

  3. Difference in doubling time in culture

    Time frame: At inclusion

    The difference in doubling time in culture (measured in days) between the MSCs of children with LA and those of children free of hemopathy. At each passage, the number of living and dead MSCs will be counted.

  4. Difference in Immunophenotypic profile

    Time frame: At inclusion

    The difference in immunophenotypic profile (cytometry, immunofluorescence) between MSCs of children with AL and those of children without hematological disease. Use of a panel of monoclonal antibodies directed against various membrane antigens (CD45, CD34, CD14, CD90, CD73, CD105).

  5. Difference in mutational profiles between MSCs and leukemia cells

    Time frame: At inclusion

    Difference in mutational profiles between MSCs and leukemia cells from children with AL. Comparison of mutations acquired by leukemic cells compared to stromal cells by an NGS-type high-throughput sequencing approach.

  6. Differences in transcriptomic signatures between MSCs and MSC subpopulations

    Time frame: At inclusion

    Differences in transcriptomic signatures between MSCs and MSC subpopulations of children with AL and those of children without hematological disease. The RNAs of the MSCs obtained after culture will be extracted then reverse-transcribed into cDNA. The quality control of the extracted RNAs will be carried out on a Bioanalyzer (Agilent). Transcriptome analysis of the MSC pool will be performed by RNA Seq/NGS. Transcriptomic identification of MSC subpopulations will be performed by single-cell RNAseq/NGS.

  7. Differences in cytokine profiles within the bone marrow

    Time frame: At inclusion

    Differences in cytokine profiles in the bone marrow and in the blood, measured in ng/mL, between children with AL and children without hematological disease.ELISA-like assay of IL-3, IL-6, IL-7, IL-8, IL-10, IL-15, TGF-bêta, IFN-gamma

Study contacts

Contact information is provided by the study sponsor or research team.

Olivier HERAULT, MD-PhD

CONTACT

[email protected]

+33(0)234378902

Wiebe de JONG, MSc

CONTACT

[email protected]

+33(0)247474680

Sponsors and collaborators

Lead sponsor

University Hospital, Tours

Other

Registry information

Official study title

Etude du Microenvironnement médullaire Dans Les Leucémies Aiguës de l'Enfant

Acronym: MILA

Important dates

Study start
2023
Primary completion
2026
Study completion
2028
First posted
Mar 30, 2023
Registry last updated
Nov 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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