Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Children with acute lymphoid leukemia B, acute lymphoid leukemia -T or acute myeloid leukemia

blood and bone marrow samples from patients with Acute Leulemia.

Biological sampling in patients

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

Biological sampling in control patients

Olivier HERAULT, MD-PhD

Wiebe de JONG, MSc

Julien LEJEUNE, MD-PhD

Emmanuel Gyan, MD-PhD

Pascale Blouin, MD

Anne Jourdain, MD

Marion Gillibert-Yvert, MD

Jill Serre, MD

Léa Bosdure, MD

Thierry ODENT, MD-PhD

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.

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.

Open-label, interventional monocentric biological study in two parallel and controlled groups

Study of the Medullary Microenvironment in Acute Childhood Leukemia

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

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.

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.

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

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.

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).

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.

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.

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

Spots Global Cancer Trial Database for biological sampling in control patients