Conditions · Metabolism (biochemistry)
Multiple myeloma !
A cancer of bone-marrow plasma cells that overproduces a single antibody (M spike) and damages bone, kidney and blood.
Updated 2026-11-01
Structures involved
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In biochemistry
- Ubiquitin–proteasome system
- Proteasome (26S, β5 subunit)
- Plasma proteins and electrophoresis
- Immunoglobulins (antibodies)
In immunology
- Bone marrow and hematopoiesis of immune cells
- B cell and plasma cell
- CD markers: the table to know
- Cancer immunotherapy: checkpoint inhibitors, CAR-T and vaccines
- Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia
- Fc receptors, BCR and TCR
In embryology
Why it happens
- Local effects of tumours and cancer cachexia
- Intracellular accumulations: cholesterol, proteins, hyaline, glycogen
- Pathologic calcification: dystrophic vs metastatic
- Tumour markers: serum and tissue, and what each one is for
- Special stains in diagnosis: Congo red, Prussian blue, PAS, Ziehl–Neelsen, Gram
What it is
A neoplasm of a plasma-cell clone in the bone marrow that makes a monoclonal immunoglobulin or light chain and causes bone lesions, anaemia, hypercalcaemia and kidney failure.
Who gets it
It accounts for about 10 % of blood cancers and 1–2 % of all cancers, with about 4 cases per 100,000 people per year. It is commoner after 60, in men and in people of African ancestry. No Colombia-specific figures were found.
Causes
- Nearly always preceded by monoclonal gammopathy of undetermined significance (MGUS) and then smouldering myeloma
- Acquired genetic changes in the plasma cell (IGH translocations, hyperdiploidy, MYC and TP53 changes)
Risk factors
- Age over 60
- Male sex
- African ancestry
- Known MGUS
- Obesity
- Family history
Pathophysiology
The plasma-cell clone fills the marrow and secretes a single immunoglobulin (IgG most often, then IgA) or light chains only. In bone, myeloma cells release RANKL and IL-6 and hold back osteoblasts (DKK1): osteoclasts resorb without repair, lytic lesions appear and calcium is released. Free light chains are filtered, precipitate with Tamm–Horsfall protein in the tubules (myeloma kidney) and can also form amyloid. The invaded marrow makes fewer red cells (anaemia) and normal immunoglobulins fall (infections). Excess protein makes red cells stack (rouleaux) and sometimes raises viscosity.
Classification
- MGUS (premalignant)
- Smouldering (asymptomatic) myeloma
- Active myeloma (with CRAB events or other criteria)
- Solitary plasmacytoma; plasma cell leukaemia
Symptoms and signs
- Bone pain, especially back and ribs
- Pathological fractures and vertebral collapse
- Fatigue and pallor from anaemia
- Thirst, confusion and constipation from hypercalcaemia
- Repeated infections
- Foamy urine or reduced urine from kidney damage
Diagnosis
- Clinical
- An older adult with bone pain, anaemia, hypercalcaemia, kidney failure or repeated infections (CRAB criteria).
- Tests
- Serum protein electrophoresis with an M spike, serum and urine immunofixation, free light chains (κ/λ ratio), Bence Jones protein in 24-hour urine; bone marrow biopsy (≥ 10 % clonal plasma cells); blood count, creatinine, calcium, albumin, β2-microglobulin and LDH for staging; cytogenetics.
- Imaging
- Low-dose whole-body CT, PET-CT or whole-body MRI for lytic lesions; X-rays show “punched-out” lesions in skull, spine, ribs and pelvis.
Treatment
- Medical
- Combinations of proteasome inhibitors (bortezomib), immunomodulators (lenalidomide), anti-CD38 antibodies (daratumumab) and corticosteroids
- Procedure
- Autologous haematopoietic stem cell transplant in fit patients
- Medical
- Bisphosphonates or denosumab to protect bone; management of hypercalcaemia and anaemia
- Procedure
- Radiotherapy for painful lesions or spinal cord compression
- Surgical
- Fixation of pathological fractures, vertebroplasty or kyphoplasty, spinal decompression
- Medical
- Cell therapies (CAR-T) and bispecific antibodies in relapsed disease
Complications
- Fractures and spinal cord compression
- Chronic kidney disease
- Severe infections
- AL amyloidosis
- Hyperviscosity
- Thrombosis (linked to some treatments)
Prognosis
Usually not curable, but current treatments have greatly extended survival; it depends on stage (revised ISS), cytogenetics and response.
Test yourself
Think of the answer, then tap the question to see it.
What does CRAB stand for in multiple myeloma?
Hypercalcaemia (C), renal failure (R), anaemia (A) and bone lesions (B): the organ damage that defines active myeloma.
Why does myeloma cause lytic lesions without a rise in alkaline phosphatase?
Myeloma cells activate osteoclasts (RANKL) and suppress osteoblasts; with no new bone formed, alkaline phosphatase does not rise.
Which electrophoresis finding points to myeloma?
An M spike: a narrow band in the γ (or β) region produced by the monoclonal immunoglobulin.
How do light chains damage the kidney?
They are filtered and form casts with Tamm–Horsfall protein that block and injure the tubules (myeloma kidney).
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Multiple myeloma: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Multiple myeloma: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Protein electrophoresis - serum: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Free Light Chains: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026).
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