Clinical trial NCT06175923: Role of BMP Pathway in MDS Progression
Official title: Role of the BMP Pathway in Myelodysplastic Syndromes Progression and in the Transition to Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Myelodysplastic Syndromes
Acute Myelogenous Leukemia
Keywords: BMP
MSC
MDS
microenvironment
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2023-12-19
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Adult patients with untreated myelodysplastic syndromes at risk of progression to acute myeloid leukemia.
* Adult patients with de novo AML

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.


Eligibility criteria: 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

Primary outcomes:
measure: Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels
timeFrame: at diagnosis, at 6 months, at 5 years
measure: Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction
timeFrame: at diagnosis, at 6 months, at 5 years
measure: Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Functional level
timeFrame: at diagnosis, at 6 months, at 5 years
measure: Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Transcriptomic level
timeFrame: at diagnosis, at 6 months, at 5 years
measure: Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level
timeFrame: at diagnosis, at 6 months, at 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hospices Civils de Lyon
Study officials:
References: