Phenotypic and Functional Study of Bone Marrow Mesenchymal Stem Cells in Waldenström Macroglobulinemia

NCT07471074 | Recruiting

• 1 other identifier: PI2025_843_0166
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Waldenström disease (WM) is defined by the presence of bone marrow lymphoplasmocytes and monoclonal immunoglobulin M (IgM). Treatment should be initiated in cases of cytopenia, tumor syndrome or when the physicochemical or immunological properties of IgM explain the occurrence of amyloidosis, cryoglobulin or neurological manifestations, which have already been extensively studied. The disease is characterized by a MYD88 emutation found in 90% of patients. However, the molecular landscape is complex: the other most frequent anomaly is a mutation in CXCR4, found in 30% of patients. This is a chronic, relapsing-remitting disease involving cells of the B lymphoid lineage, whose behavior is normally influenced by the presence of their specific target and signals from their environment. Indeed, around WM tumor cells, numerous lymphocyte population abnormalities have been reported (excess of atypical extra follicular B lymphocytes, decrease in naive B, T or NK populations, increase in certain suppressive subpopulations (Treg, TFH). In a mouse model, excess Tregs cells appear to interact with WM cells via the CD40/CD40ligand axis. Mast cells may also promote proliferation of WM malignant cells via the same axis. Myeloid and monocytic populations have an inflammatory profile. Furthermore, increased angiogenesis may counteract the effects of bone marrow hypoxia (which itself prevents WM cell proliferation and adhesion to mesenchymal cells). In addition, several cytokines probably play an important role: CXCL12, highly expressed in the marrow of WM patients, may play a role due to the high frequency of CXCR4 activating mutations. CXCL12 is also involved in the adhesion of WM cells to fibronectin. WM cells have increased expression of Very late antigen-4 (VLA4), which co-interacts with CXCR4 and promotes WM cell adhesion to medullary mesenchymal stem cells (MSCs) and endothelial cells. The CCL5/GLI2/IL6 axis also appears to be important. Other factors have also been suggested: Interleukin 21, Blys and abnormal angiogenic factors. MSCs could play an important role in these multiple cellular \& extracellular factors via CCL5, then IL6. CXCL12, activation of the Eph-B2-(expressed by WM cells) Ephrin B2 (expressed by MSCs) pathway. The role of MSCs and abnormalities in these cells has already been recognized in certain leukemias, leading to therapeutic strategies that are now envisaged to target not the neoplastic cell but its microenvironment. However, in WM, the interactions between these cells and the clonal cells of the disease remain unknown today. cellular factors via CCL5, then IL6. CXCL12, activation of the Eph-B2-(expressed by WM cells) Ephrin B2 (expressed by MSCs) pathway.

Conditions

Waldenström Macroglobuloinemia

Keywords

Waldenström Macroglobuloinemia

Outcome Measures

Primary Outcomes (1)

• Variation of transcriptome between both groups

  Comparison of the transcriptome of MSCs from patients with WM with that of MSCs from healthy subjects

  2 years

Secondary Outcomes (2)

• variation of MSC culture between both groups

  2 years

• Variation of MSC cell adhesion between both groups

  2 years

Study Arms (2)

patients with WM

EXPERIMENTAL

Genetic: sample of bone marrow cells

healthy volunteers

ACTIVE COMPARATOR

Genetic: sample of bone marrow cells

Interventions

sample of bone marrow cells GENETIC

For all these patients, information will be collected from the common hemopathy description form (derived from the clinical annotations used in SLP-rares). A 5 ml sample of bone marrow cells will be collected for MSC study. A study of CXCL12 polymorphism (-801GA) will be conducted

healthy volunteers; patients with WM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with WM, meeting the diagnostic criteria defined at the 2nd WM Workshop, revised at the 9th international workshop.
• Patients requiring treatment within 3 months according to the recommendations defined at the 2nd Workshop on WM.
• Patients having given their consent for this study.
• Affiliation to a social security scheme.

You may not qualify if:

• Patients with other chronic lymphoid hemopathies. Particular care should be taken to exclude other closely related lymphoplasmacytic proliferations, especially marginal zone lymphomas.
• Patients with WM who have undergone histological transformation to a lymphoma other than diffuse large B- cell lymphoma.
• Absence of consent for this study.

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead

Study Sites (1)

CHU Amiens

Amiens, 80480, France

RECRUITING

Central Study Contacts

Pierre MOREL

CONTACT

33+3 22 45 54 19; morel.pierre@chu-amiens.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 13, 2026
• Study Start: February 10, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)