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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, ĪNp73, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDS patients | Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization:
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| AML patients | Adult patients with suspected de novo acute myeloid leukemia at initial management |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels | 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 | at diagnosis, at 6 months, at 5 years |
| Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction | 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 | at diagnosis, at 6 months, at 5 years |
| Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Functional level | 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) | at diagnosis, at 6 months, at 5 years |
| Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Transcriptomic level | 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.). | at diagnosis, at 6 months, at 5 years |
| Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maƫl MD Heiblig | Contact | 0478864340 | +33 | Mael.heiblig@chu-lyon.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospices Civils de Lyon | Lyon | 69229 | France |
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| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
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Bone marrow aspirates will be collected, both at diagnosis and 6-month follow-up.
|
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). |
| at diagnosis, at 6 months, at 5 years |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |