Role of BMP Pathway in MDS Progression

NCT06175923 | Not Yet Recruiting

• 1 other identifier: 69HCL22_0491
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes; Acute Myelogenous Leukemia

Keywords

BMP; MSC; MDS; microenvironment

Outcome Measures

Primary Outcomes (5)

• 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

  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

Study Arms (2)

MDS patients

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)

Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care

AML patients

Adult patients with suspected de novo acute myeloid leukemia at initial management

Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care

Interventions

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.

AML patients; MDS patients

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• Frontier MDS/myeloproliferative syndromes including chronic myelomonocytic leukemia
• MDS and AML having already benefited from cytotoxic treatment including hydroxycarbamide, azacytidine, intensive chemotherapy
• Pregnant or breastfeeding women
• Patients under legal protection measure

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hospices Civils de Lyon

Lyon, 69229, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bone marrow aspirates will be collected, both at diagnosis and 6-month follow-up.

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Maël MD Heiblig

CONTACT

0478864340; Mael.heiblig@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 19, 2023
• Study Start: January 27, 2024
• Primary Completion (Estimated): January 27, 2029
• Study Completion (Estimated): January 27, 2034
• Last Updated: January 23, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)