Mutations can occur in the chromosomes of people with multiple myeloma, a type of bone marrow cancer. Cytogenetics examines how these mutations affect the prognosis and treatment options for individuals with this cancer.

Chromosomes are thread-like structures in a cell’s nucleus that contains genes. These chromosomes can develop mutations, which may cause disease.

Cytogenetics refers to the study of chromosomes, including their links to disease. The field is vital for diagnosing, managing, and understanding the risk and prognosis for people with cancers.

Multiple myeloma (MM) is a cancer of the plasma cells, which are mainly in the bone marrow. People with MM commonly have chromosomal mutations, and doctors use cytogenetics to determine the best stage, risk, and treatment for this condition.

Keep reading to learn more about cytogenetics and MM.

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MM is a type of cancer that affects plasma cells, a type of immune cell. Individuals with MM may experience a variety of symptoms and outcomes. These symptoms can include bone pain, fatigue, and weakness of the arms or legs.

The International Myeloma Working Group (IMWG) recommends cytogenetic testing for people with MM for the initial diagnosis and relapse. This is because chromosomal mutations influence disease progression and outcomes of individuals with the disease.

Doctors divide cytogenetic mutations for MM into two classes: primary and secondary.


These are mutations that occur during the monoclonal gammopathy of undetermined significance (MGUS) stage, a noncancerous condition that affects plasma cells.

However, according to the National Cancer Institute, around 1% of people with MGUS will develop multiple myeloma each year.

The primary mutations typically affect the immunoglobulin genes, which make antibodies to fight disease. For example, it can cause parts of a chromosome to break away and reattach to a different chromosome. Doctors call these translocation mutations.

The most common primary mutation is trisomic mutation, which causes three chromosomes to develop instead of two.


Secondary mutations occur later in the disease or during its progression — they can develop in any MM subtypes and may overlap. This means a person can have several secondary cytogenetic mutations.

Secondary mutations can also be monosomic, where the mutation causes one member of a chromosome pair to be missing. For example, people with MM could be missing a chromosome from numbers 13–17.

Risk categories

A 2015 study classified individuals with MM into four risk categories depending on the presence of these mutations:

  • high risk, where mutations could include a deletion on chromosome 17
  • intermediate risk, which could include a trisomy
  • standard risk, which includes mutations that are not in the intermediate or high risk categories
  • low risk, where no mutations are present

A 2020 update on these risk categories included additional mutations as being high risk, where the presence of two mutations refers to double-hit myeloma, while three or more is triple-hit myeloma.

Several factors influence a person’s prognosis and treatment options for MM, including age, renal function, and cancer stage. However, cytogenetic mutations are another major influence on the likely outcome of MM.

A 2019 study found that people in intermediate and high-risk groups had a lower likelihood of survival than those in low-risk groups.

Low-risk groups had a 75% chance of survival over 5 years. In contrast, individuals in the intermediate and high-risk groups had a 50–75% and lower than 50% chance of survival, respectively.

The study also found that those in high-risk groups had a 6–15-fold higher risk of death than those in low-risk groups.

Clinical trials have found that people with different cytogenetic mutations show varied responses to treatments and therapies. These different responses can affect the chances of survival.

For example, a 2015 study found that some individuals with a deletion on chromosome 17 responded well to treatment with pomalidomide and dexamethasone. The outcome of those with this mutation was similar to those without this chromosome deletion following treatment. This is significant because people with this deletion tend to have a worse prognosis than those without it.

Additionally, a 2020 study found that individuals with specific translocation mutations responded better to treatment with medication than those with other mutations.

Cytogenetic abnormalities can also influence how the MM develops, which affects prognosis.

For example, the same 2020 study found that renal problems are higher in people with specific translocations. Another study found that 25% of individuals with translocations of chromosomes 14–16 experienced renal failure as the only sign of myeloma at the time of diagnosis.

Learn more about MM outlook.

Treatment for MM varies depending on factors that include a person’s age, kidney function, cancer stage, and whether they are eligible for stem cell transplants. Cytogenetics also influences treatment options, including in those with newly diagnosed MM.


There are various treatments for MM, including:

  • chemotherapy
  • corticosteroids, such as dexamethasone
  • immunomodulating agents, such as thalidomide
  • proteasome inhibitors, such as bortezomib
  • histone deacetylase inhibitors
  • monoclonal antibodies, such as daratumumab
  • antibody-drug conjugates
  • nuclear export inhibitor

Doctors typically combine these drugs to improve their effectiveness. For example, a healthcare professional may recommend bortezomib, lenalidomide, and dexamethasone for individuals with a new diagnosis of MM.

Doctors may also recommend different treatments depending on a person’s cytogenetic risk group. The IMWG recommends bortezomib and carfilzomib for people in high-risk groups to improve treatment responses and survival.

Radiation therapy

Radiation therapy treats bone areas affected by MM damage. These are usually in cases where chemotherapy is not working, there is severe pain, or there is a risk of bone fractures, potentially leading to paralysis.

Stem cell transplant

Stem cell transplant involves taking stem cells from someone without MM for use in people with MM. A 2014 study recommends using cytogenetic risk categories following stem cell transplant therapy.

Learn more about stem cell transplants for MM.

Chimeric antigen receptor-cell therapy

Chimeric antigen receptor-cell therapy involves removing T-cells, altering their structure, and replacing them in a person’s blood. The treatment can support the immune system to fight cancerous cells in individuals with MM.

Learn more about treatment options for MM.

Cytogenetics can improve prognosis, treatment response, and care for people with MM.

Doctors will use cytogenetic risk categories to determine the best treatment approaches. Some cytogenetic mutations will require specific treatments or increase the risk of complications.