Phenotypic and Functional Study of Bone Marrow Mesenchymal Stem Cells in Waldenström Macroglobulinemia (SLP-rares-CSM)

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.

Study Overview

• Status: Recruiting
• Conditions: Waldenström Macroglobuloinemia
• Intervention / Treatment: Genetic: sample of bone marrow cells

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre MOREL; Phone Number: 33+3 22 45 54 19; Email: morel.pierre@chu-amiens.fr

Study Locations

• France
  • Amiens, France, 80480
    • Recruiting
    • CHU Amiens
    • Contact: Pierre MOREL, MD; Phone Number: 03.22.45.54.19; Email: morel.pierre@chu-amiens.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Patients under court protection, subjects participating in another study with an exclusion period still in progress at pre-inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: healthy volunteers	Genetic: sample of bone marrow cells; 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
Experimental: patients with WM	Genetic: sample of bone marrow cells; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
variation of MSC culture between both groups	Perform a comparison between bulk culture and culture after FACS/magnetic bead sorting of MSCs, assessing their viability and characterization.	2 years
Variation of MSC cell adhesion between both groups		2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Waldenström Macroglobuloinemia
• Other Study ID Numbers: PI2025_843_0166

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