Targeting Multiple Myeloma through the Biology of Long-Lived Plasma Cells

Multiple myeloma (MM) is a hematological malignancy of terminally differentiated bone marrow (BM) resident B lymphocytes known as plasma cells (PC). PC that reside in the bone marrow include a distinct population of long-lived plasma cells (LLPC) that have the capacity to live for very long periods...

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Bibliographic Details
Published inCancers Vol. 12; no. 8; p. 2117
Main Authors Utley, Adam, Lipchick, Brittany, Lee, Kelvin P., Nikiforov, Mikhail A.
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 30.07.2020
MDPI
Subjects
Antibodies
Antigens
Autophagy
Biology
Bone marrow
Bortezomib
Care and treatment
Cell survival
Chemokines
Cytokines
Dexamethasone
Endoplasmic reticulum
Epigenetics
Hematology
Immunomodulation
Lymphocytes B
Malignancy
Metabolism
Multiple myeloma
Patient outcomes
Phagocytosis
Plasma
Plasma cells
Proteasomes
Protein folding
Respiration
Review
Steroid hormones
Transcription factors
United States
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Summary:Multiple myeloma (MM) is a hematological malignancy of terminally differentiated bone marrow (BM) resident B lymphocytes known as plasma cells (PC). PC that reside in the bone marrow include a distinct population of long-lived plasma cells (LLPC) that have the capacity to live for very long periods of time (decades in the human population). LLPC biology is critical for understanding MM disease induction and progression because MM shares many of the same extrinsic and intrinsic survival programs as LLPC. Extrinsic survival signals required for LLPC survival include soluble factors and cellular partners in the bone marrow microenvironment. Intrinsic programs that enhance cellular fidelity are also required for LLPC survival including increased autophagy, metabolic fitness, the unfolded protein response (UPR), and enhanced responsiveness to endoplasmic reticulum (ER) stress. Targeting LLPC cell survival mechanisms have led to standard of care treatments for MM including proteasome inhibition (Bortezomib), steroids (Dexamethasone), and immunomodulatory drugs (Lenalidomide). MM patients that relapse often do so by circumventing LLPC survival pathways targeted by treatment. Understanding the mechanisms by which LLPC are able to survive can allow us insight into the treatment of MM, which allows for the enhancement of therapeutic strategies in MM both at diagnosis and upon patient relapse.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12082117