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

Overview

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.

Interventions

• 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

Primary outcome measures

• Variation of transcriptome between both groups [Time frame: 2 years]

Secondary outcome measures (2)

• variation of MSC culture between both groups [Time frame: 2 years]
• Variation of MSC cell adhesion between both groups [Time frame: 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Screening

Study locations

France · 1 center

• CHU Amiens — Amiens

Identifiers

NCT: NCT07471074 · PI2025_843_0166

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗