APRIL and TACI interact with syndecan‐1 on the surface of multiple myeloma cells to form an essential survival loop

Moreaux, Jérôme; Sprynski, Anne-Catherine; Dillon, Stacey R.; Mahtouk, Karène; Jourdan, Michel; Ythier, Arnaud; Moine, Philippe; Naeije, Robert; Jourdan, Éric; Rossi, Jean François; Klein, Bernard

doi:10.1111/j.1600-0609.2009.01262.x

Cited by 105 publications

(100 citation statements)

References 52 publications

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“…Previous investigation showed that soluble APRIL binding to MM cells was dependent on heparan sulfate (HS) chains from CD138. 18 We further show that total abrogation of sulfation by short-term treatment with sodium chlorate in MM cell lines inhibited soluble APRIL binding (Figure 4a). In addition to HS, CD138 also bears another sulfated glycan structure in the form of chondroitin sulfate chains.…”

Section: In Vivomentioning

confidence: 57%

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Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

Matthes

Mckee²,

Dunand-Sauthier³

et al. 2015

Leukemia

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Multiple myeloma (MM) is a non-curable tumor developing in the bone marrow (BM). The BM microenvironment rich in hematopoietic precursors is suspected to have a role in MM development. Here we show that a proliferation-inducing ligand (APRIL) mediated in vivo MM promotion. In MM-infiltrated BM, APRIL originated from differentiating myeloid cells with an expression peak in precursor cells. Notably, APRIL expression stayed stable in BM despite MM infiltration. The pool of APRIL-producing cells changed upon MM infiltration. Although CD16(+) mature myeloid cells constituted about half of the APRIL-producing cells in healthy BM, CD16(-) Elastase(+) myeloid precursor cells were predominant in MM-infiltrated BM. Myeloid precursor cells secreted all the APRIL they produced, and binding of secreted APRIL to MM cells, strictly dependent of heparan sulfate carried by CD138, resulted in an in situ internalization by tumor cells. This indicated APRIL consumption by MM in BM. Taken together, our data show that myelopoiesis dysregulation characterized by an increased proportion of precursor cells occurs in MM patients. Such dysregulation correlates with a stable expression of the MM-promoting factor APRIL in infiltrated BM

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Section: In Vivomentioning

confidence: 57%

“…In MM, APRIL increases cell cycle progression and survival. [17][18][19] In a mouse preclinical model, a soluble form of TACI reduces tumor development in fetal bones implanted into immunodeficient mice.…”

Section: Introductionmentioning

confidence: 99%

Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

Matthes

Mckee²,

Dunand-Sauthier³

et al. 2015

Leukemia

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show abstract

“…The receptors for APRIL and/or (63), reflecting the fact that BAFF has a 1000-fold weaker affinity for BCMA than APRIL. Furthermore, CD138 on PCs is an important costimulatory molecule for APRIL-TACI but not for BAFF-TACI or APRIL-BCMA signaling, as it harvests APRIL from the environment and presents it to TACI (63).…”

Section: Malignant Pcsmentioning

confidence: 99%

Pathogenic Long-Lived Plasma Cells and Their Survival Niches in Autoimmunity, Malignancy, and Allergy

Winter

Dame

Jundt

et al. 2012

The Journal of Immunology

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Long-lived plasma cells survive in a protected microenvironment for years or even a lifetime and provide humoral memory by establishing persistent Ab titers. Long-lived autoreactive, malignant, and allergen-specific plasma cells are likewise protected in their survival niche and are refractory to immunosuppression, B cell depletion, and irradiation. Their elimination remains an essential therapeutic challenge. Recent data indicate that long-lived plasma cells reside in a multicomponent plasma cell niche with a stable mesenchymal and a dynamic hematopoietic component, both providing essential soluble and membrane-bound survival factors. Alternative niches with different hematopoietic cell components compensate fluctuations of single cell types but may also harbor distinct plasma cell subsets. In this Brief Review, we discuss conventional therapies in autoimmunity and multiple myeloma in comparison with novel drugs that target plasma cells and their niches. In the future, such strategies may enable the specific depletion of pathogenic plasma cells while leaving the protective humoral memory intact.

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“…BCMA has significantly higher affinity for APRIL than for BAFF (Kd range nM vs μM) [30]. Unlike BAFF, which also binds BAFF-R besides BCMA and TACI, APRIL binds to BCMA and TACI associated with heparan sulfate proteoglycan (HSPG), that is, CD138/syndecan-1 (Figure 1), suggesting a more PC-specific role of APRIL than BAFF [31]. In addition, serum BCMA is Targeting B-cell maturation antigen in multiple myeloma Review higher in MM patients versus healthy donors, suggesting a new biomarker for monitoring disease status and overall survival of MM patients [32].…”

Section: Bcma Is An Ideal Antigen For Targeted Immunotherapy For MMmentioning

confidence: 99%

Targeting B-Cell Maturation Antigen in Multiple Myeloma

2015

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Novel effective immunotherapies are needed for patients with multiple myeloma (MM), since disease recurrence remains a major obstacle. B-cell maturation antigen (BCMA), a cell surface protein universally expressed on malignant plasma cells , has emerged as a very selective antigen to be targeted in novel treatments for MM. We here first review BCMA-related biology, and then highlight the recent clinical development of a novel afucosylated anti-BCMA monoclonal antibody conjugated with monomethyl auristatin F via noncleavable linker (GSK2857916). Chimeric antigen receptor-expressing T cells targeting BCMA may also induce specific and durable anti-MM responses by patients’ own effector cells. Clinical trials testing these two approaches (NCT02064387, NCT02215967) are currently ongoing in relapsed and refractory MM patients.

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APRIL and TACI interact with syndecan‐1 on the surface of multiple myeloma cells to form an essential survival loop

Cited by 105 publications

References 52 publications

Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

Pathogenic Long-Lived Plasma Cells and Their Survival Niches in Autoimmunity, Malignancy, and Allergy

Targeting B-Cell Maturation Antigen in Multiple Myeloma

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