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Other Lymphoma Types

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Double Hit (DHL), Triple Hit (THL) & Double Expressor Lymphoma

Double and triple hit lymphomas refer to genetic changes called rearrangements involved in your lymphoma. Double expressor refers to the amount of proteins on your lymphoma cells.

Double and triple hit lymphoma refer to genetic changes called rearrangements that can happen in people with high-grade B-cell lymphomas. These rearrangements happen in genes called MYC and BCL that are responsible for regulating the growth and control of B-cell lymphocytes, including when they should be destroyed.

Double expressor lymphoma is different from double and triple hit lymphomas because there is no genetic rearrangement in double expressor lymphoma. However, there is an overexpression (or too much) of the MYC and BCL proteins on the lymphoma cells.

These changes can make the lymphoma more difficult to treat with a higher chance of relapsing after treatment. This may not be the case for everyone though, and will depend on other factors such as other genetic changes and proteins on your lymphoma cells.

On this page:

What is high-grade lymphoma?

Click to download Double hit, Triple hit & Double Expressor (High-grade B-Cell) Lymphoma brochure.

High-grade lymphomas are lymphomas that grow and spread quickly throughout your body. Because the lymphoma cells grow so quickly, they are unable to develop or function the way they should, so they often look very different from your normal healthy B-cells.

High-grade lymphomas that can have double or triple hit rearrangements or a double expression include Diffuse Large B-cell Lymphoma (DLBCL) and other high-grade B-cell lymphomas. For information on these subtypes, please click the links below.

Understanding your lymphoma genetics

Cytogenetic tests are done to check for genetic variances that may be involved in your disease. For more information on these please see our section on understanding your lymphoma genetics further down on this page. The tests used to check for any genetic mutations are called cytogenetic tests. These tests look to see if you have any changed in chromosomes and genes.

We usually have 23 pairs of chromosomes, and they are numbered according to their size. If you have DHL or THL, the genes (MYC and BCL genes) on your chromosomes have been rearranged.

What are genes and chromosomes

Each cell that makes up our body has a nucleus, and inside the nucleus are the 23 pairs of chromosomes. Each chromosome is made from long strands of DNA (deoxyribonucleic acid) that contain our genes. Our genes provide the code needed to make all the cells and proteins in our body, and tells them how to look or act. 

Changes in your genes and chromosomes can help work out your diagnosis, and can affect your treatment options

Overview of double hit (DHL) and triple hit (THL) lymphoma

Double hit (DHL) and triple hit (THL) lymphomas are when you have a high-grade lymphoma and a change in your two (double hit) or three (triple hit) of your genes.  The change that happens in these genes is called a rearrangement and can increase your chance of getting lymphoma and make it harder to treat in some cases.

Is triple hit worse than double hit lymphoma?

In triple hit lymphoma you have a rearrangement in your MYC and BCL2 genes, but you will also have a rearrangement in another gene called BCL6.

It used to be thought that having triple hit lymphoma was worse than having double hit lymphoma, and that triple hit was more aggressive and harder to treat. 

However, with more research we now know that is not the case. In fact, the World Health Organisation (W.H.O.) suggests that triple hit lymphoma no longer be considered as a separate consideration, and be managed in the same way a double hit lymphoma is managed.

Are all double hit lymphomas the same?

Double hit lymphoma only refers to whether you have a rearrangement in your MYC and your BCL2 genes. 
 
However, there are many other genetic changes that can happen when you have lymphoma. There are also different types of proteins that may be present on your lymphoma cells. So really, no double hit lymphoma is the same.
 
Whether your lymphoma can be cured, or how likely it is to relapse (come back) after treatment, depends on all the different genetic changes and proteins involved in your individual lymphoma as well as other factors.
 
Talk to your doctor about your individual changes and what these mean for your lymphoma and treatment options.

Overview of double expressor lymphoma (DEL)

Double expressor lymphoma means you have extra MYC and BCL proteins on your lymphoma cells, however you do not have a rearrangement in your genes.

These proteins can stop cancer cells from being destroyed and result in lymphoma developing and becoming aggressive.

Some double expressor lymphomas can be more difficult to treat, but this will depend on other factors such as if you have any other genetic changes or other proteins on your lymphoma cells.

Rearrangement and protein expression in Double & Triple Hit, and Double Expressor Lymphomas

 

MYC Rearrangement
BCL2 Rearrangement
BCL6 Rearrangement
Overexpression of MYC and BCL proteins
Double Hit

YES

YES

No

Usually, but not always

Triple Hit

YES

YES

YES

Usually, but not always

Double Expressor

No

No

No

YES

Ask your doctor to explain you individual changes and how these may impact your treatment.

 

Proto-oncogenes and Oncogenes

MYC and BCL are proto-oncogenes. When you have a rearrangement in these genes, they can become oncogenes. Click on the flip boxes to learn what proto-oncogenes and oncogenes are. 

Proto-oncogenes

Scroll over the card to learn more

Proto-oncogenes

Proto- oncogenes are normal genes that help different cells in our body grow, develop, multiply and repair or die when they are damaged, diseased or are no longer needed.
If a proto-oncogene is mutated or has a re-arrangement they can become oncogenes.

Oncogenes

Scroll over card to learn more

Oncogene

Oncogenes are genes that when activated, can cause cells to become cancerous. They make proteins that prevent cancerous cells from destroying themselves, and instead let them continue to grow and multiply.

What do MYC and BCL Genes & Proteins do?

MYC Gene & Protein

The MYC gene provides the information for the MYC protein to be made and work effectively. The MYC protein helps cells to grow and prevents from them from dying. This is good when you have healthy cells that are working properly. However, when there is a rearrangement in the MYC gene, or you have too much of the MYC protein, cancerous cells can develop and keep growing too. 

MYC gene rearrangements, or too much MYC protein stop cancer cells from dying and allow them to keep growing and making new cancer cells.

BCL Genes and Proteins

BCL stands for B-cell lymphoma – There are several different subtypes of the BCL genes and proteins. BCL is more specific than MYC in that it is targeted to the development, function and survival of B-cell lymphocytes. 

When BCL2 and BCL6 are working effectively as they should, they keep a good balance of healthy B-cell lymphocytes.

Having a rearrangement in your BCL2 gene may mean you have more aggressive lymphoma, and increased chance of relapsing than if you have a rearrangement in your BCL 6 gene.

BCL2

 

The BCL2 gene provides the information for the BCL2 protein to be made.

When there is a rearrangement of the BCL2 gene, or an overexpression of the BCL2 proteins, B-cell lymphocytes continue to grow and multiply. If B-cell lymphocytes are growing too quickly they are unable to develop properly or, if they have cancerous changes, they can result in lymphoma as they continue to make more cancerous B-cell lymphocytes.

BCL6 

The BCL6 gene provides the information for the BCL6 protein to be made.

When rearranged or mutated, BCL6 can impact the way tumour suppressor genes work. Tumour suppressor genes are specialised to recognise and destroy cancer cells. 

BCL6 can prevent tumour suppressor genes from being able to recognise and destroy cancer cells. It can also prevent follicular helper T-cell lymphocytes from developing. These T-cells are needed to help B-cells work effectively to fight cancer.

Testing for Double / Triple Hit and Double Expressor

If you have a high-grade lymphoma your doctor may wish to do further tests on your biopsies to see if you have any genetic rearrangements or double expressing proteins. The test is called Flourescence In Situ Hybridization (FISH) and looks at the different genetic markers, such as MYC and BCL on your biopsy samples. 

The FISH test is not covered by the Medicare benefits scheme, however in some cases may be covered as part of your diagnostic workup. However, it is only able to be completed at some centres across Australia, so in some cases there may be out of pocket cost for you to get this done. The cost can vary depending on where you get it done. 

It’s important to know that the results may not make any difference to the treatment you are offered, and there are other “prognostic indicator” tools that can be used instead of the FISH test. Your doctor can use these other tests to look at how well you are likely to respond to treatment. These are internationally recognized tools that have been tried and tested to be a good indicator of your likely response to treatment. 

Often, your treatment will not change even if you have DHL/THL or double expressor lymphoma, but in some cases it might. If the treatment would change if you had these variations, then you may consider getting the test done.  

Treatment for DHL, THL and DEL

Often the treatment for DHL, THL and DEL are similar treatments given in High-grade B-cell Lymphoma and Diffuse Large B-cell Lymphoma. In some cases, your haematologist may choose a more aggressive type of treatment for you. However, there are no large-scale clinical trials that provide evidence that more aggressive treatment will be better for you.

Your choice of treatment should be a decision made with your haematologist or oncologist once they have all the necessary information about your lymphoma, and have discussed the benefits and risks of each treatment to you, and your chance of cure or relapse.

For more information on treatment please see the links below

For more info see
Lymphoma Treatments
For more info see
Side effects of treatment
For more info see
Diffuse Large B-cell Lymphoma

Summary

  • Double Hit (DHL), Triple hit (THL) and Double expressor (DEL) are found in people with high-grade lymphomas such as Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma.
  • Double hit and triple hit lymphomas refer to genetic changes called rearrangements that occur in MYC and BCL genes.
  • Double expressor lymphoma means there is an over expression (too much) of the MYC and BCL proteins, but no genetic rearrangement.
  • Triple hit lymphoma has similar considerations to a double hit lymphoma with MYC gene and BCL2 gene rearrangements.
  • These variations in your lymphoma can make it more aggressive and harder to treat than other subtypes of DLBCL and other High grade B-cell lymphomas.
  • You have a higher chance of relapse with you have a DHL, THL or DEL variation to your lymphoma.
  • Treatment of DHL, THL and DEL may be similar to that of people with other subtypes of DLBCL and High-grade B-cell lymphoma.
  • Testing for DHL, THL and DEL can be expensive as it is not covered by the Medicare benefits scheme, so you may need to pay for it yourself.
  • Talk to your doctor about your individual variations and what these mean for you.
  • You are not alone, if you would like to chat about your lymphoma and options, call our Lymphoma Care Nurses. Click on the Contact Us button at the bottom of the screen for details.

Support and information

Learn more about your blood tests here – Lab tests online

Learn more about your treatments here – eviQ anticancer treatments – Lymphoma

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