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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''TNFRSF17''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. 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 integra ...

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 growth ...

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 Serum may refer to: Biology and pharmacology *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity *Serous fluid, any clear bodily fluid Places *Serum, Ind ...

of normal patients and generally elevated in patients with

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

(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 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 inserted into the plasm ...

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 advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with the B-cell activating factor TNFSF13B. A conserved domain at the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.

Clinical significance

TNFRSF17 is implicated in

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce 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). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

s, and

(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, chromosomes anomalies, leukemias, solid tumours, and cancer ...

,).

As a drug target

An antibody-drug conjugate Belantamab mafodotin (GSK2857916) has been evaluated in patients with relapsed/refractory multiple myeloma. Belantamab mafodotin was approved in the United States in August 2020 for the treatment of patients with relapsed or refractory multiple myeloma who have received at least four prior therapies. Chimeric antigen receptor (CAR) T cells have emerged as an important therapy for multiple myeloma after first reports in preclinical and phase I clinical studies. A Phase 1b/2 study of JNJ-4528, a 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 has been completed. ALLO-715 is a

CAR-T In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific ...

therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA). , it is undergoing

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

for the treatment of

. On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715. ALLO-715 is being investigated at

Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a cancer treatment and research institution in Manhattan in New York City. MSKCC is one of 72 National Cancer Institute– designated Comprehensive Cancer Centers. Its main campus is ...

and the

Mayo Clinic Mayo Clinic () is a Nonprofit organization, private American Academic health science centre, academic Medical centers in the United States, medical center focused on integrated health care, healthcare, Mayo Clinic College of Medicine and Science ...

as part of the UNIVERSAL trial for

, on its own and in conjunction with the selective

gamma secretase Gamma secretase is a multi-subunit protease complex, an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most ...

inhibitor

nirogacestat Nirogacestat, sold under the brand name Ogsiveo, is an anti-cancer medication used for the treatment of desmoid tumors. It is a selective gamma secretase enzyme inhibitor, inhibitor that is taken by mouth. Nirogacestat was approved for medi ...

Function

Interactions

Clinical significance

As a drug target

References

External links

Further reading