Acute Myelogenous Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
BMP, MSC, MDS, microenvironment
Brief summary
Myelodysplastic syndromes (MDS) are hematological cancers that can progress to acute myelogenous leukemia (AML). The involvement of the microenvironment in the maintenance, resistance and evolution of MDS is increasingly described. The Bone Morphogenetic Protein (BMP) pathway is involved in numerous functions, including self-renewal of the hematopoietic stem cell compartment and the regulation of hematopoiesis, via interaction with bone marrow stromal cells. Investigators have demonstrated its involvement in chronic myeloid leukemia (CML) and AML, in particular via the activation of TWIST1, ΔNp73, NANOG; it is responsible for an increased state of quiescence of certain cancer stem cells and their resistance. Preliminary results based on the analysis of large databases suggest that the BMP pathway is also altered early in MDS. This study explores the alteration of this pathway in MDS and its involvement in the transformation into AML. If appropriate, the BMP pathway could constitute a very promising therapeutic target to combat transformation into AML.
Interventions
BIOLOGICALCollection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care
When bone marrow is collected as part of a patient's care (diagnosis, follow-up, suspected AML/MDS hemopathy), one or two additional EDTA tubes of marrow are collected. Certain hematological data (NFP, genetic and molecular characteristics) will be collected in anonymized form and correlated with the BMP pathway alterations measured.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization Or * Adult patient with suspicion of de novo acute myeloid leukemia at initial treatment
Exclusion criteria
* Frontier MDS/myeloproliferative syndromes including chronic myelomonocytic leukemia * MDS and AML having already benefited from cytotoxic treatment including hydroxycarbamide, azacytidine, intensive chemotherapy * Patients objecting to their inclusion in the study * Pregnant or breastfeeding women * Patients under legal protection measure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels | at diagnosis, at 6 months, at 5 years | Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein, transcriptomic and functional levels : Marrow plasma to study the concentration of cytokines of interest BMP2 and BMP4 |
| Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction | at diagnosis, at 6 months, at 5 years | Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein, transcriptomic and functional levels : Medullary blood mononuclear cells: expression of membrane receptors BMPRIA and BMPRIB by RT-QPCR and flow cytometry, expression of cytokines BMP2 and BMP4 (RT-QPCR), degree of phosphorylation of SMAD intermediates by western blot and/or flow cytometry, expression of BMP pathway target genes by RT-QPCR |
| Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Functional level | at diagnosis, at 6 months, at 5 years | Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at functional level : Medullary MSCs will be cultured and studied from functional angle (culture, colony-forming units tests, long term culture initiating colony) |
| Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Transcriptomic level | at diagnosis, at 6 months, at 5 years | Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at transcriptomic level : Medullary MSCs will be cultured and studied from transcriptomic angle (expression of receptors, BMP cytokines, target genes, etc.). |
| Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level | at diagnosis, at 6 months, at 5 years | Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein level : Medullary MSCs will be cultured and studied from protein angle (cytokines present in the supernatant). |
Countries
France
Contacts
Primary ContactMaël MD Heiblig
Outcome results
None listed