Myeloma is a cancer that affects B cells, the immune cells responsible for the production of antibodies. Normal B cells develop in bone marrow, where myeloma grows. Multiple myeloma arises when the cancer cells travel through the body and form tumors in several different bones. Affected bones may become brittle as the malignant cells proliferate and alter the chemical equilibrium in the marrow.1
In 2016, the American Cancer Society estimates that 30,330 new multiple myeloma cases will be diagnosed and 12,650 cancer deaths due to multiple myeloma would occur.2 There are approximately 55,000 people affected in the United States.3Multiple myeloma is the second most common hematologic malignancy in the United States, but it accounts for only about 1% of all cancers.4 Multiple myeloma is rarely diagnosed in individuals under the age of 45.5
Below is a list of the information found within this section:
- Immune Cells
- Risk Factors
- Detection and Diagnosis
- Pathology Report and Staging
- Tumor Biology
- Multiple Myeloma Resources
- Section Summary
The immune system works to recognize and eliminate foreign material and pathogens. Multiple myeloma is a cancer of B lymphocytes,a type of immune cell. In adults, B cells form and mature in the bone marrow. When activated, B cells produce Y-shaped proteins (antibodies) that are part of the immune response. Antibodies then bind to their target, killing the target and clearing it from the body. The many different B cells in our bodies each make only one type of antibody. B cells that have become activated to produce antibodies are called 'plasma cells'.6
In multiple myeloma a plasma B cell becomes genetically damaged and divides (proliferates) uncontrollably. The cancerous cells over-produce antibodies that may accumulate in the bone marrow. The altered plasma cells also stimulate bone cells called osteoclasts. Osteoclasts produce enzymes that dissolve the bone structure and cause some of the symptoms associated with the disease, including pain and disfigurement. Because B cell normally move around the body, the cancerous cells are able to get in the blood stream and metastasis is very common. Frequently, multiple tumors are present in different bones. 5
Multiple myeloma (MM) is more common in men than women. The ratio of male to female diagnosis is about 1.4 : 1. The American Cancer Society predicts that 11,170 men and 9,010 women will be diagnosed with this disease in 2010. Multiple myeloma is also twice as common in African Americans than in Caucasians. 7 The cause for this difference is unknown.
- Age - Risk of developing MM is higher for the elderly. The median age of diagnosis is 67.
- Gender - Men are more likely to develop MM than women.
- Race - African Americans are more likely to develop MM than other ethnicities.
- Radiation exposure
- Family history - Prior family history of myeloma increases risk MM development.
- Jobs with exposure to petroleum products
- Obesity - Studies suggest that obesity may increase risk.
- Other plasma cell diseases - People with diseases affecting B cells, including plasmacytoma and monoclonal gammopathy of unknown significance (MGUS) are more likely to develop MM.
Multiple Myeloma is often difficult to diagnose because the vague symptoms that may be present in the early stages of the disease are often mistaken for other illnesses. In many patients, symptoms do not appear until the disease is at an advanced stage. Routine blood tests may be able to detect abnormal blood protein levels.
- bone pain
- chronic fatigue
- blood cell (hematologic) abnormalities- i.e. anemia, a condition when the patient doesnt have enough healthy red blood cells
- nervous system abnormalities (neuropathy)
- repeated infections
- loss of kidney function (renal failure)
- elevated levels of calcium in the blood (hypercalcemia)
- unexplained weight loss
- elevated levels of antibodies (immunoglobulin) or other proteins in the blood and/or urine
Watch an interview about a multiple myeloma survivor Ginny Johnston
Multiple myeloma results in the overproduction of antibodies by B cells in the tumors. The antibodies can be detected in samples of blood or urine from the patient. Another protein present on the surface of B cells (beta2-microglobulin) is frequently elevated in multiple myeloma. Multiple myeloma may also be detected by bone marrow biopsies.10
The National Comprehensive Cancer Network (NCCN) recommends PET and CT scans. CT scan may detect alterations and damage to bone structures. Whole-body MRI is another option. MRI images provide valuable information and may allow for greater accuracy in diagnosis.10
Multiple myeloma is commonly found in the vertebrae, skull, pelvic bones, ribs, humerus, and femur. Dentists may help identify the disease if it affects the jaw region of the skull.
Gene expression profiling is under investigation as a way of categorizing multiple myeloma cases. Expression profiling is a way to categorize the cancer cells based on their biologic properties. Profiling and molecular markers are increasingly important and common tools to guide treatment decisions.1112
Learn more about cancer detection methods. Methods covered include PET, CT and MRI.
The staging system used for multiple myeloma is the "International Staging System" or ISS. This system is less complex than previous systems. The size and mass of the tumor is no longer included. Staging is based on levels of two blood proteins, serum albumin and beta2-microglobulin.3
- Stage 1 : Serum B-2 Microglobulin less than 3.5mg/L and Serum Albumin greater than 3.5g/dL
- Stage 2 : *not classified as either stage 1 or 3*
- Stage 3 : Serum B-2 Microglobulin greater than 5.5mg/L
The malignant B plasma cells in Multiple Myeloma generally migrate to the bone marrow. Once in, they attach to the supporting structures and cells (matrix). The matrix supports the cells as they proliferate. Within the bone marrow, numerous growth factors and other proteins influence the growth of the cells.13
Some of the growth factors and cytokines that play a role in multiple myeloma are:
- Interleukin 6 (IL-6) - a cytokine secreted by T cells. Stimulates other white blood cells (leukocytes), including B cells.14
- Tumor Necrosis Factor alpha (TNFα) - a cytokine mainly secreted by macrophages. Stimulates the immune system and induces inflammation.
- Vascular Endothelial Growth Factor (VEGF) - a growth factor secreted by cells in the bone marrow. Promotes angiogenesis and therefore the growth of tumors.
- Insulin-like Growth Factor I (IGF-1) - a growth factor that activates the AKT pathway. Promotes growth and inhibits cell death.
- Stromal Derived Factor 1 alpha (SDF-1α) - a cytokine that regulates the migration of blood cells to the bone marrow.
- Hepatocyte Growth Factor (HGF) - a glycoprotein produced by cells in the bone marrow. Promotes adhesion of cells to the matrix and may regulate cell migration.15
Genes that have been implicated in multiple myeloma include:
- PTTG-1 - a proto-oncogene coding for a transcription factor associated with progression in multiple myeloma5
- PI3K - a gene that codes for a kinase which promotes cell division.16
- AKT - an proto-oncogene. The protein product inhibits cell death. 17
- GILZ - a tumor supressor gene which promotes cell death when activated by glucocorticoids. It is inhibited by the activities of PI3K and AKT. 17
As our focus is on the biology of the cancers and their treatments, we do not give detailed treatment guidelines. Instead, we link to organizations in the U.S. that generate the treatment guidelines.
The National Comprehensive Cancer Network (NCCN) lists the following treatments for multiple myeloma:
- Chemotherapy: included the proteasome inhibitor bortezomib (Velcade®)
- Combination chemotherapy
- Autologous Stem Cell Transplantation
Learn more about the treatment for Multiple Myeloma at the Winship Cancer Institute of Emory University.
Information about clinical trials:
- General clinical trial information from CancerQuest
- Click here for information about clinical trials at the Winship Cancer Institute of Emory University
- Click here for information about clinical trials from the National Cancer Institute.
- Click here for information about clinical trials from Georgia Clinical Trials Online.
- Results from malignant B cells that migrate to the bone marrow.
- ACS estimates that 20,180 new cases of MM will be diagnosed and 10,650 deaths will be reported in a year.
- Only accounts for 1% of all cancers
- Current 5-year survival rate is 30%
- B plasma cells are a type of differentiated lymphoid cell
- Plasma cells normally produce antibodies, proteins that help combat various pathogens, each cell produces a specific antibody
- In MM, the cancerous plasma cells become uncontrollable and produce large amounts of a non-helpful antibody.
- The cells migrate to the bone marrow where they recieve growth signals
- Typically the tumor in the bone marrow spreads to other parts of the body.
- Male to Female ratio of diagnoses is 1.4 : 1
- ACS estimates 11,170 men and 9,010 women will be diagnosed in 2010
- For reasons unknown MM is twice as likely in African Americans as in Caucasians.
- Age, gender, race, radiation exposure, family history, working in oil-related industries, weight, other plasma cell diseases may also increase risk
- Symptoms may not be apparent until a late stage of the disease
- It is important to get routine blood work done
- Symptoms may include: chronic pain in the bone, chronic fatigue, anemia, neuropathy, recurring infections, hypercalcemia.
Detection and Diagnosis
- Blood or Urine tests can detect abnormalities in antibody protein levels
- NCCN recommends CT scans
- Biopsy is an option
- Dental professionals can identify some cases (jaw)
Staging and Pathology
- New staging system called the "International Staging System" is now used.
- The ISS is simpler than previous systems
- Staging is now based on the levels of Beta-2 microoglobulin in the blood of the patient.
Multiple Myeloma Tumor Biology
- MM development is dependent on gene mutation and growth factors.
- The bone marrow provides growth signals to the tumor and prevents cell death.
- Some of the cytokines involved are: IL-6, TNFa, VEGF, IGF-1, SDF-1a, HGF
- Some of the genes involved are: PTTG-1, PI3K, AKT, GILZ
- Treatment success is very dependent on the stage of the cancer
- A primary option is Hemopoeitic Stem Cell transplant
- Chemotherapy with bortezomib and doxorubicin is frequently used.
- 1. Chiriva-Internati M, Ferraro R, Prabhakar M, Yu Y, Baggoni L, Moreno J, Gagliano N, Portinaro N, Jenkins MR, Frezza EE, Hardwicke F, D'Cunha N, Kast W, Cobos E. "The pituitary tumor transforming gene 1 (PTTG-1): an immunological target for multiple myeloma." J Transl Med. 2008 Apr 2;6:15. [PUBMED]
- 2. American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016. [http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf]
- 3. a. b. Katzel JA, Hari P, Vesole DH. "Multiple myeloma: charging toward a bright future." CA Cancer J Clin. 2007 Sep-Oct;57(5):301-18. [PUBMED]
- 4. Pinto LS, Campagnoli EB, Leon JE, Lopes MA, Jorge J. "Maxillary lesion presenting as a first sign of multiple myeloma: case report." Med Oral Patol Oral Cir Bucal. 2007 Sep 1;12(5):E344-7. [PUBMED]
- 5. a. b. c. Chiriva-Internati M, Ferraro R, Prabhakar M, Yu Y, Baggoni L, Moreno J, Gagliano N, Portinaro N, Jenkins MR, Frezza EE, Hardwicke F, D'Cunha N, Kast W, Cobos E. "The pituitary tumor transforming gene 1 (PTTG-1): an immunological target for multiple myeloma." J Transl Med. 2008 Apr 2;6:15. [PUBMED]
- 6. Roitt IM, Brostoff J, Male DK. "Immunology" Gower Medical Publishing Ltd. 1985. London. Pg 2.3
- 7. a. b. Cancer Facts and Figures 2010. American Cancer Society. [http://www.cancerquest.org/sites/default/files/assets/pdf/facts%26figures2010.pdf]
- 8. Alexander DD, Mink PJ, Adam HO, Cole P, Mandel JS, Oken MM, and Trichopoulos D. Multiple myeloma: A review of the epidemiologic literature. International Journal of Cancer. 2001; 120:40-61. [PUBMED]
- 9. American Cancer Society. "Detailed Guide: Multiple Myeloma". Copyright 2010 American Cancer Society. Site accessed October 2010. [http://www.cancer.org/Cancer/MultipleMyeloma/DetailedGuide/multiple-myeloma-detection]
- 10. a. b. Schmidt GP, Schoenberg SO, Reiser MF, Baur-Melnyk A. "Whole-body MR imaging of bone marrow." Eur J Radiol (2005 Jul);55(1):33-40. [PUBMED]
- 11. Henry T. and R. Fonseca. "Genomics and proteomics in multiple myeloma and Waldenström macroglobulinemia." Curr Opin Hematol. 2007 Jul;14(4):369-74 [PUBMED]
- 12. PL Bergsagel. "Individualizing therapy using molecular markers in multiple myeloma." (2007) Clin Lymphoma Myeloma. Apr;7 Suppl 4:S170-4. [PUBMED]
- 13. Hideshima T, Podar K, Chauhan D and KC Anderson. "Cytokines and signal transduction." (2005) Best Pract Res Clin Haematol. 18(4):509-24. [PUBMED]
- 14. Huston A and GD Roodman."Role of the microenvironment in multiple myeloma bone disease." (2006) Future Oncol. Jun;2(3):371-8 [PUBMED]
- 15. Holt RU, Fagerli UM, Baykov V, Ro TB, Hov H, Waage A, Sundan A, Borset M. "Hepatocyte growth factor promotes migration of human myeloma cells". Haematologica. 2008 Apr;93(4):619-22. [PUBMED]
- 16. Grugan KD, Ma C, Singhal S, Krett NL, Rosen ST. "Dual regulation of glucocorticoid-induced leucine zipper (GILZ) by the glucocorticoid receptor and the PI3-kinase/AKT pathways in multiple myeloma." J Steroid Biochem Mol Biol. 2008 Jun;110(3-5):244-54. Epub 2008 Apr 20. [PUBMED]
- 17. a. b. Grugan KD, Ma C, Singhal S, Krett NL, Rosen ST. "Dual regulation of glucocorticoid-induced leucine zipper (GILZ) by the glucocorticoid receptor and the PI3-kinase/AKT pathways in multiple myeloma." J Steroid Biochem Mol Biol. 2008 Jun;110(3-5):244-54. Epub 2008 Apr 20. [PUBMED]