B-cell maturation antigen (BCMA or BCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the TNFRSF17

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. TNFRSF17 is a

cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...

of the

TNF receptor The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve gro ...

superfamily which recognizes

B-cell activating factor B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B and CD257 among other names, is a protein that in humans is encoded by the ''TNFSF13B'' gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) a ...

(BAFF). Serum B-cell maturation antigen (sBCMA) is the cleaved form of BCMA, found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM).

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature

B lymphocyte B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation.

Interactions

TNFRSF17 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with the B-cell activating factor TNFSF13B. A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.

Clinical significance

TNFRSF17 is implicated in

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

s, and multiple myeloma (see the "Mitelman Database" and the

Atlas of Genetics and Cytogenetics in Oncology and Haematology The Atlas of Genetics and Cytogenetics in Oncology and Haematology, created in 1997 by Jean-Loup Huret (with bioinformatics by Philippe Dessen) is a collection of resources on genes, Chromosome abnormality, chromosomes anomalies, leukemias, solid ...

,).

As a drug target

antibody-drug conjugate Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 phar ...

GSK2857916 (belantamab mafodotin) demonstrated activity in patients with relapsed/refractory multiple myeloma, previously treated with an immunomodulatory drug, proteosome inhibitor, or who were intolerant/refractory to an anti-CD38 monoclonal antibody. The primary toxicities were keratopathy, thrombocytopenia, and anemia.

Belantamab mafodotin Belantamab mafodotin, sold under the brand name Blenrep, is a medication for the treatment of relapsed and refractory multiple myeloma. The most common adverse reactions include keratopathy (corneal epithelium change on eye exam), decreased vi ...

(GSK2857916) was approved for medical use in the United States in August 2020. A Phase 1b/2 study of CAR-T cell therapy directed against BCMA in myeloma patients refractory to a proteasome inhibitor or immunomodulatory drug, and who had received an anti-CD38 antibody showed a 91% overall response rate. Main toxicities were cytokine release syndrome and cytopenias.

Function

Interactions

Clinical significance

As a drug target

References

External links

Further reading