Study of the Medullary Microenvironment in Acute Childhood Leukemia (MILA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoid Leukemia; Acute Myeloid Leukemia in Children
• Intervention / Treatment: Procedure: Biological sampling in patients; Procedure: Biological sampling in control patients

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 Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olivier HERAULT, MD-PhD; Phone Number: +33(0)234378902; Email: olivier.herault@univ-tours.fr
• Study Contact Backup: Name: Wiebe de JONG, MSc; Phone Number: +33(0)247474680; Email: w.dejong@chu-tours.fr

Study Locations

• France
  • Tours, France, 37044
    • Not yet recruiting
    • Service d'hématologie biologique-CHRU TOURS
    • Contact: Olivier HERAULT, MD-PhD; Phone Number: +33(0)247474721; Email: olivier.herault@univ-tours.fr
    • Principal Investigator: Olivier HERAULT, MD-PhD
  • Tours, France, 37044
    • Recruiting
    • Service d'onco-hématologie pédiatrique -CHRU Tours
    • Contact: Julien LEJEUNE, MD-PhD; Email: j.lejeune@chu-tours.fr
    • Principal Investigator: Julien LEJEUNE, MD-PhD
    • Sub-Investigator: Emmanuel Gyan, MD-PhD
    • Sub-Investigator: Pascale Blouin, MD
    • Sub-Investigator: Anne Jourdain, MD
    • Sub-Investigator: Marion Gillibert-Yvert, MD
    • Sub-Investigator: Jill Serre, MD
    • Sub-Investigator: Léa Bosdure, MD
  • Tours, France, 37044
    • Recruiting
    • Service de chirurgie orthopédique pédiatrique -CHRU TOURS
    • Contact: Thierry ODENT, MD-PhD; Phone Number: +33(0)247473822; Email: t.odent@chu-tours.fr
    • Principal Investigator: Thierry ODENT, MD-PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 15 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• for patients with AL:

  1. Child with acute lymphoblastic or myeloblastic leukemia at diagnosis
  2. Not having received prior hematological treatment
  3. Aged 1 to 15 years old
  4. Whose 2 parents, or the holder of parental authority, have signed a consent enlightened.
  5. Affiliated patient or beneficiary of a social security scheme.

• Control group patients:

  1. Child undergoing orthopedic surgery exposing the bone marrow (osteotomy of the pelvis).
  2. Aged between 1 and 15 years old.
  3. Having no pathology of hematological origin.
  4. Not having received any treatment that could interfere with the functioning of the bone marrow.
  5. Whose 2 parents or the holder of parental authority have signed a consent enlightened.
  6. Affiliated patient or beneficiary of a social security scheme.

Exclusion Criteria:

• for patients with AL:

  1. Patient under 1 year old and over 15 years old.
  2. Contraindication to myelogram.
  3. Absence of signature of the informed consent by the 2 parents or the holder of parental authority.
  4. Patients with relapsed acute lymphoblastic or myeloblastic leukemia.
  5. Having received prior hematological treatments.
  6. Parents with physical or mental condition not allowing to understand the informed consent.

• Control group patients

  1. Patient under 1 year old and over 15 years old.
  2. Having an underlying haematological pathology.
  3. Absence of signature of the informed consent by the 2 parents or the holder of parental authority.
  4. Having received prior hematological treatments.
  5. Parents with physical or mental condition not allowing to understand informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients with acute leukemias; Children with acute lymphoid leukemia B, acute lymphoid leukemia -T or acute myeloid leukemia	Procedure: Biological sampling in patients; blood and bone marrow samples from patients with Acute Leulemia.
Other: Control group; Children without blood diseases	Procedure: Biological sampling in control patients; blood and bone marrow samples from children undergoing orthopedic surgery exposing the bone marrow.(osteotomy of the pelvis).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen Consumption Rate	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.	At inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Extra Cellular Acidification Rate	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.	At inclusion
Difference in Reactive Oxygen Species	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	At inclusion
Difference in doubling time in culture	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.	At inclusion
Difference in Immunophenotypic profile	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).	At inclusion
Difference in mutational profiles between MSCs and leukemia cells	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.	At inclusion
Differences in transcriptomic signatures between MSCs and MSC subpopulations	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.	At inclusion
Differences in cytokine profiles within the bone marrow	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	At inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Study Director: Olivier HERAULT, MD-PhD, University hospital of Tours; Principal Investigator: Julien LEJEUNE, MD-PhD, University hospital of Tours

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2023
• Primary Completion (Estimated): October 25, 2026
• Study Completion (Estimated): October 24, 2028

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 17, 2023
• First Posted (Actual): March 30, 2023

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: DR220254-MILA; 2022-A02570-43 (Registry Identifier: IdRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No