Role of BMP Pathway in MDS Progression

Not yet recruiting

• Conditions: Acute Myelogenous Leukemia; Myelodysplastic Syndromes
• Interventions: Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care

• Registration Number: NCT06175923
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-11
• Study First Submitted: 2023-11-29
• Study First Submitted QC: 2023-12-08
• Study First Posted: 2023-12-19
• Last Update Submitted: 2024-01-19
• Last Update Posted: 2024-01-23
• Study Start: 2024-01-27
• Primary Completion: 2029-01-27
• Study Completion: 2034-01-27

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MDS patients	Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care	Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization: * one or more cytopenias, * and/or dysplasia of one or more lines, * and/or bone marrow blastosis * and/or sideroblasts in medullary crowns * and/or genetic/cytogenetic abnormalities characteristic of MDS. * Whatever the R-IPSS stage (Revised International Prognostic Scoring System) * No history of cytotoxic treatment (hydroxycarbamide, azacytidine)
AML patients	Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care	Adult patients with suspected de novo acute myeloid leukemia at initial management

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (1)

Hospices Civils de Lyon; 🇫🇷 Lyon, France