Lymphoma is a type of cancer originating in lymphocytes, white blood cells that form part of the body’s immune system. These cells are found in lymph nodes, the spleen, thymus, bone marrow, and other parts of the body. Double-Hit Lymphoma (DHL) is an aggressive and uncommon subtype of diffuse large B-cell lymphoma (DLBCL). It is characterized by rapid progression and often presents with advanced disease at diagnosis.
Understanding Double-Hit Lymphoma
Double-Hit Lymphoma is defined by specific genetic alterations within lymphoma cells. These alterations typically involve rearrangements, or translocations, in two genes: MYC and at least one of the BCL2 or BCL6 genes. A rearrangement occurs when pieces of chromosomes break off and combine abnormally, leading to altered gene function. The presence of these two specific genetic changes gives the lymphoma its “double-hit” designation.
The MYC gene plays a role in cell cycle progression, protein synthesis, and metabolism; changes to this gene can lead to rapid growth of lymphoma cells. The BCL2 gene normally regulates cell death, and its alteration in DHL can result in lymphoma cells surviving longer. Similarly, BCL6 influences cell activation and DNA damage response. These genetic changes are acquired within cancer cells during a person’s lifetime, rather than being passed down through generations.
The Genetic Basis and Hereditary Link
While Double-Hit Lymphoma (DHL) is characterized by specific genetic mutations, these are overwhelmingly somatic mutations. Somatic mutations occur in individual cells after conception and are not present in germline cells (sperm or egg), meaning they cannot be inherited by offspring. These mutations arise during a person’s lifetime due to various factors, leading to lymphoma development.
In contrast, hereditary conditions are caused by germline mutations, present in every cell of the body because they are inherited from a parent. For DHL, the defining “double-hit” rearrangements in MYC and BCL2 or BCL6 are not typically found in the germline. This means DHL is generally not considered a hereditary cancer. While some individuals may have an inherited predisposition to certain types of lymphoma due to germline mutations in other genes, these are distinct from DHL’s specific genetic hallmarks.
Other Risk Factors for Double-Hit Lymphoma
Since Double-Hit Lymphoma is not typically inherited, other factors contribute to its development. Age is a significant risk factor, as DHL primarily affects older adults, with a median age often between 62 and 74 years. A slight male predominance is also observed in DHL cases.
A weakened immune system can also increase the risk of developing lymphoma, including DHL. This includes individuals with conditions such as HIV/AIDS or those who have received organ transplants and are on immunosuppressive medications. Certain autoimmune diseases have also been associated with an increased risk of non-Hodgkin lymphoma. Some studies have also investigated potential links between exposure to specific chemicals, such as certain herbicides and insecticides, and radiation exposure, though these connections are still being explored.