Role of BMP Pathway in MDS Progression
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age20+
SponsorHospices Civils de Lyon
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial population
* Adult patients with untreated myelodysplastic syndromes at risk of progression to acute myeloid leukemia. * Adult patients with de novo AML
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care
Biological/VaccineWhen 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: MDS patients1 intervention
Group B: AML patients1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
at diagnosis, at 6 months, at 5 years2
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
Time frame
at diagnosis, at 6 months, at 5 years3
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)
Time frame
at diagnosis, at 6 months, at 5 years4
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.).
Time frame
at diagnosis, at 6 months, at 5 yearsSponsors and contacts
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Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: