Role of BMP Pathway in MDS Progression

Myelodysplastic Syndromes Clinical Trial

— BMP-MDS  

Official title:

Role of the BMP Pathway in Myelodysplastic Syndromes Progression and in the Transition to Acute Myeloid Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06175923
• Other study ID #: 69HCL22_0491
• Status: Not yet recruiting
• Start date: January 27, 2024
• Est. completion date: January 27, 2034

Study information

• Verified date: November 2023
• Source: Hospices Civils de Lyon
• Contact: Maël MD Heiblig
• Phone: 0478864340
• Email: Mael.heiblig[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 27, 2034
• Est. primary completion date: January 27, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Biological:
• Collection 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.

Locations

Country	Name	City	State
France	Hospices Civils de Lyon	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level	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