Role of BMP Pathway in MDS Progression (BMP-MDS)

January 19, 2024 updated by: Hospices Civils de Lyon

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Lyon, France, 69229
        • Hospices Civils de Lyon
        • Contact:
          • Maël MD HEIBLIG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels
Time Frame: 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
at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction
Time Frame: 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
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
Time Frame: 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)
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
Time Frame: 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.).
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
Time Frame: 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).
at diagnosis, at 6 months, at 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 27, 2024

Primary Completion (Estimated)

January 27, 2029

Study Completion (Estimated)

January 27, 2034

Study Registration Dates

First Submitted

November 29, 2023

First Submitted That Met QC Criteria

December 8, 2023

First Posted (Actual)

December 19, 2023

Study Record Updates

Last Update Posted (Actual)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 19, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL22_0491

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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