MIF Involvement in AML

NCT03918655 | Active Not Recruiting

• 1 other identifier: PRT-K16055
• Study Type: observational
• Target: 186
• Locations: 1 country
• Sites: 1

Brief 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

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia.; Macrophage migration inhibitory factor; Hematopoietic stem cell

Outcome Measures

Primary Outcomes (1)

• MIF concentration in the blood and the bone marrow and MIF RNA expression

  MIF concentration in the blood and the bone marrow (measured by ELISA), and MIF RNA expression assessed by quantitative RT-PCR in unsorted and sorted cell populations in order to determine which AMLs have pre-leukemic stem cells that overexpress MIF

  At Day 0

Secondary Outcomes (4)

• Overall and leukemia free survivals

  patient complete remission until the last patient visit, for 36 months period

• The number of patients in complete remission with persistent pre-leukemic stem cells that over express MIF

  at Day 0 and at time of complete remission or relapse until the last patient visit for a 36 months period.

• Rate of MIF inhibitors and anti-MIF antibodies will be tested in preclinical models

  at Day 0 and at time of complete remission or relapse until the last patient visit for a 36 months period.

• The molecular mechanisms of MIF overexpression

  at Day 0 and at time of complete remission or relapse until the last patient visit for a 36 months period.

Study Arms (2)

Patient newly diagnosed with AML (prospectively)

Patient newly diagnosed with AML in Saint Antoine hospital or Tours University hospital

Patient diagnosed with AML (retrospectively)

Patient diagnosed with AML in Saint Antoine hospital in 2015 to 2019

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

the participants will be adult patients (over 18) newly diagnosed with AML at Saint-Antoine Hospital or Tours University Hospital.

You may qualify if:

• Patient newly diagnosed with AML in Saint Antoine hospital or Tours University hospital
• Age \> or equal 18 years old,
• Written informed consent signed

You may not qualify if:

• Patient without social insurance

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• CHRU Tours: centre Hospitalier Universitaire de Tours: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator

Study Sites (1)

Laboratoire d'hématologie Hôpital Saint Antoine

Paris, 75012, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Only standard care blood and bone marrow samples will be used in the study : * Blood samples for biochemistry, blood cell counts, immunophenotyping, cytogenetics, molecular biology analyses, and tumor bank cryopreservation * Bone marrow samples for immunophenotyping, cytogenetics, molecular biology analyses, and tumor bank cryopreservation

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• François DELHOMMEAU, PharmaD, PhD

  Assistance Publique- Hôpitaux de Paris, Sorbonne université, Inserm

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: April 17, 2019
• Study Start: July 7, 2019
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-04

Locations

FR (1)