Blood cancer develops when something goes wrong in the DNA of blood-forming cells, usually in the bone marrow. A genetic mutation causes these cells to grow out of control, crowding out healthy blood cells and disrupting the body’s ability to fight infection, carry oxygen, or control bleeding. The specific trigger behind that initial mutation varies, and in many cases, multiple factors work together over time.
There are three main categories of blood cancer: leukemia (affecting white blood cells and bone marrow), lymphoma (affecting the lymphatic system), and myeloma (affecting plasma cells). While each type behaves differently, the underlying causes overlap significantly.
How Blood Cancer Starts in the Bone Marrow
Your bone marrow constantly produces new blood cells from stem cells in a process called hematopoiesis. When a stem cell acquires a DNA mutation, it can begin producing abnormal copies of itself. These mutated cells may multiply faster than normal, resist the signals that tell old cells to die, or fail to mature into functioning blood cells. The result is a buildup of defective cells that eventually interferes with normal blood production.
This process is rarely caused by a single mutation. Progression from an initial genetic change to a full-blown blood cancer involves multiple steps, with additional mutations accumulating over time. Environmental triggers like infections and chronic inflammation can accelerate this progression by giving mutated cells a survival advantage over healthy ones. For instance, chronic inflammation has been shown to enhance the fitness of cells carrying mutations in the TP53 gene, a key tumor suppressor, promoting the development of certain bone marrow cancers.
A Common Precursor: Clonal Hematopoiesis
Many people carry blood stem cells with cancer-associated mutations without ever developing blood cancer. This condition, called clonal hematopoiesis of indeterminate potential (CHIP), becomes increasingly common with age. A single mutated stem cell expands into a larger population of identical cells, but these cells still function relatively normally.
CHIP carries roughly a 0.5 to 1% risk per year of progressing to blood cancer. While that represents about a 13-fold increase compared to people without CHIP, the absolute risk remains small. Most people with CHIP never develop a malignancy because additional mutations in other genes are needed to trigger a true cancer. Think of CHIP as a first step on a long staircase, not a diagnosis in itself.
Chemical and Radiation Exposure
Benzene is the most well-established chemical cause of blood cancer. The EPA classifies it as a known human carcinogen, and occupational exposure has been directly linked to increased rates of leukemia. People who work in industries that manufacture or use benzene, such as petroleum refining, chemical production, and rubber manufacturing, face the highest exposure levels. Even at low concentrations, long-term benzene exposure damages blood-forming cells in the bone marrow.
Ionizing radiation is another proven cause. Studies of atomic bomb survivors in Japan found a nonlinear relationship between radiation dose and leukemia risk, with elevated risk persisting 55 years after exposure, particularly for acute myeloid leukemia. Research has also shown significantly increased rates of both acute myeloid and acute lymphoblastic leukemia after cumulative childhood radiation doses below 100 millisieverts, a relatively modest amount. Occupational exposure in nuclear industry workers, radiological researchers, and airline flight crews has also been linked to increased cancer risk. Bone marrow cells that produce red blood cells are especially sensitive to radiation damage, with measurable effects at doses as low as 1 to 2 gray.
Viruses That Target Blood Cells
Certain viruses can directly contribute to blood cancer by infecting lymphocytes, the white blood cells of the immune system, and altering their growth behavior.
Epstein-Barr virus (EBV), the virus behind mononucleosis, is linked to several types of lymphoma, including Burkitt’s lymphoma. EBV infects B cells and can change how they grow by switching on and off various cellular genes. In most people, the immune system keeps infected cells in check, and the virus causes no lasting harm. But in people with weakened immune systems, whether from organ transplantation, HIV/AIDS, or inherited immune deficiencies, EBV-infected cells are far more likely to progress toward lymphoma.
HTLV-1, a virus found primarily in parts of Japan, the Caribbean, and sub-Saharan Africa, infects T cells and is the established cause of adult T-cell leukemia/lymphoma. Like EBV, infection with HTLV-1 is most often asymptomatic, and only a small fraction of infected people eventually develop cancer. The virus doesn’t insert a cancer gene into the cell. Instead, it produces proteins that gradually alter the host cell’s growth controls, and over years or decades, additional mutations accumulate to complete the transformation.
Previous Cancer Treatment
One of the more unsettling causes of blood cancer is prior treatment for a different cancer. Certain chemotherapy drugs and radiation therapy can damage the DNA of bone marrow stem cells, leading to what’s called therapy-related leukemia or myelodysplastic syndrome.
The timeline depends on the type of treatment. Alkylating agents, a class of chemotherapy drugs used against many solid tumors, carry a latency period of 4 to 7 years before a secondary blood cancer appears. Another class of drugs called topoisomerase inhibitors tends to cause leukemia sooner, typically within 1 to 3 years. The risk is dose-dependent: among patients with germ cell tumors, fewer than 3% developed secondary leukemia at lower doses of one common drug, but that figure jumped above 11% at higher doses. Secondary blood cancers have been documented in survivors of Wilms tumor (appearing 1 to 6 years after treatment) and pediatric sarcomas (1 to 8 years after diagnosis).
Autoimmune Conditions
Chronic activation of the immune system appears to increase the risk of blood cancers, and several autoimmune diseases carry notably elevated rates.
- Sjögren’s syndrome carries the most dramatic risk. A meta-analysis of over 47,000 patients found that people with this condition face an 11.6-fold higher risk of blood cancers overall. Non-Hodgkin lymphoma risk is 13 to 14 times higher, and Hodgkin lymphoma and multiple myeloma risk is 8 to 9 times higher than in the general population.
- Systemic lupus erythematosus (SLE) is most strongly associated with non-Hodgkin lymphoma, which occurs 4 to 5 times more frequently in lupus patients. Elevated risks also exist for Hodgkin lymphoma, leukemia, and myelodysplastic syndromes.
- Rheumatoid arthritis (RA) is linked to increased rates of B-cell and T/NK-cell non-Hodgkin lymphoma, acute myeloid leukemia, and myelodysplastic syndromes. A rare type called large granular lymphocyte leukemia is especially associated with RA, particularly in patients with Felty’s syndrome.
The connection likely involves both the underlying chronic inflammation itself, which can promote the expansion of mutated blood cells, and some of the immunosuppressive medications used to treat these conditions.
Inherited Genetic Syndromes
Most blood cancers are not directly inherited, but certain genetic syndromes substantially raise the risk. Down syndrome, caused by an extra copy of chromosome 21, predisposes children to both acute myeloid leukemia and acute lymphoblastic leukemia through mechanisms that aren’t fully understood but appear to involve multiple factors working together.
Li-Fraumeni syndrome, caused by an inherited mutation in the TP53 gene, increases the risk of many cancers including both types of acute leukemia. Fanconi anemia and dyskeratosis congenita, both bone marrow failure syndromes, also carry elevated blood cancer risk because these conditions impair the body’s ability to repair DNA damage in blood-forming cells. More recently, mutations in a gene called DDX41 have been identified as a cause of familial blood cancers, often appearing as leukemia later in life after additional mutations accumulate in the bone marrow.
Obesity and Smoking
Lifestyle factors play a role as well, though their contribution is more modest than chemical or radiation exposure. Obesity has been linked to a 73% increase in the odds of developing a precursor condition to multiple myeloma, called MGUS, after controlling for age, sex, race, education, and income. MGUS is a buildup of abnormal plasma cells that can, over time, progress to full myeloma. Heavy smoking and short sleep duration are also associated with higher rates of detectable MGUS.
The connection between obesity and blood cancer likely involves chronic low-grade inflammation in fat tissue, which creates the kind of environment that favors the expansion of mutated cells. Tobacco smoke contains benzene and other carcinogens that reach the bone marrow through the bloodstream, providing a more direct route to DNA damage in blood-forming cells.
Why Most Cases Have No Single Cause
For the majority of people diagnosed with blood cancer, there is no single identifiable cause. The disease typically results from an unlucky accumulation of genetic changes over a lifetime, driven by a combination of inherited susceptibility, environmental exposures, immune system activity, and simple chance. Age is the strongest single risk factor for most blood cancers precisely because the longer cells divide, the more opportunities there are for errors to accumulate. Understanding the known risk factors can help explain why blood cancers happen, but for any individual case, the honest answer is often that multiple forces converged over many years.