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NCT Number: NCT06175923

Role of BMP Pathway in MDS Progression

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.

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Key information

Conditions

Myelodysplastic Syndromes Acute Myelogenous Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

20 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospices Civils de Lyon

Lyon, 69229, France

Location contact

Maël MD HEIBLIG

CONTACT

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

  1. 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

  2. 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

  3. 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)

  4. 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.).

  5. 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Maël MD Heiblig

CONTACT

[email protected]

0478864340 ext. +33

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

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

Acronym: BMP-MDS

Important dates

Study start
2024
Primary completion
2029
Study completion
2034
First posted
Dec 19, 2023
Registry last updated
Jan 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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