MedTrace Logo

MIF Involvement in AML

NCT03918655 · Status: ACTIVE_NOT_RECRUITING · Type: OBSERVATIONAL · Enrollment: 186

Last updated 2025-04-02

No results posted yet for this study

Summary

This study is an observational study of MIF involvement in retrospectively and prospectively included adult acute myeloid leukemia (AML). Standard care samples collected at diagnosis, after one course of treatment, at time of remission controls, and at time of relapse will be used.

The first objective is to determine which AMLs have pre-leukemic stem cells that overexpress MIF. Cytogenetic and molecular (NGS) profiling will be performed at diagnosis. Blood and bone marrow plasma, as well as bone marrow mononuclear cells will be collected and stored. The expression of MIF and its receptor (CD74 and CXCR4) will be analysed. Their prognostic value will be also tested.

The second objective is to test whether patients in complete remission have persistent pre-leukemic stem cells that overexpress MIF. Blood and bone marrow plasma, bone marrow mononuclear cells from patients in complete remission will be collected. MIF, CD74, and CXCR4 expression by hematopoietic cells at time of diagnosis and remission will be compared to determine which patients have a persistent overexpression/secretion of MIF. In the meantime, the persistence of initiating lesions in complete remission samples will be tested by NGS, digital PCR, FISH, or RT-PCR methods.

The third objective is to develop a pre-clinical model to target MIF in immuno-compromised mice (NSG mice) transplanted with primary AML cells and cells with pre-leukemic lesions. TET2 depletion leads to MIF over-expression/secretion by hematopoietic cells and improved multi-lineage NSG-repopulation capacity. MIF inhibitors and anti-MIF antibodies will be tested in these pre-clinical TET2-depleted models. Xenotransplantation of selected primary AML samples and xenotransplantation of TET2 depleted hematopoietic stem cells into NSG mice will be used.

The fourth objective is to understand how MIF is deregulated in pre-leukemic stem cells and how the MIF-dependent crosstalk between mesenchymal stromal cells (MSCs) and pre-leukemic stem cells or normal hematopoietic cells works.

The molecular mechanisms of MIF overexpression will be analyzed in hematopoietic stem and progenitor cells from normal and leukemic bone marrow, with a focus on cells depleted in TET2 or DNMT3A. To study the cross-talk between hematopoietic stem and progenitor cells, pre-leukemic stem cells, and bone marrow MSCs, co-culture experiments will be performed using available MSC cell lines and primary MSCs from healthy donors.

Conditions

Sponsors & Collaborators

  • Institut National de la Santé Et de la Recherche Médicale, France

    collaborator OTHER_GOV

  • CHRU Tours: centre Hospitalier Universitaire de Tours

    collaborator UNKNOWN

  • Gustave Roussy, Cancer Campus, Grand Paris

    collaborator OTHER

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Principal Investigators

  • François DELHOMMEAU, PharmaD, PhD · Assistance Publique- Hôpitaux de Paris, Sorbonne université, Inserm

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-07-07
Primary Completion
2025-06-30
Completion
2025-06-30

Countries

  • France

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03918655 on ClinicalTrials.gov