The main cause of blood cancer is DNA mutations that accumulate in blood-forming stem cells over a person’s lifetime. These mutations are overwhelmingly acquired rather than inherited, with up to 90% of all cancers arising from genetic changes that happen by chance as cells divide over time. Only about 10% may be linked to inherited genetic predispositions. While no single trigger explains every case, the core mechanism is the same: mutations give a blood cell a growth advantage, allowing it to multiply uncontrollably and crowd out healthy cells.
How Mutations in Blood Stem Cells Start Cancer
Your bone marrow contains stem cells that continuously produce red blood cells, white blood cells, and platelets. Every time these stem cells divide, there’s a small chance of a copying error in their DNA. Most of these errors are harmless. But occasionally, a mutation lands in a gene that controls cell growth, giving that one cell a competitive advantage over its neighbors. It begins to expand, creating a clone of genetically identical cells.
A single mutation usually isn’t enough. Research in Cell Stem Cell indicates that up to five separate “driver” mutations may be needed before a cell gains enough of a competitive edge to dominate the bone marrow and become cancerous. These hits accumulate over years or decades, which is why blood cancers are far more common in older adults. The median age at diagnosis for leukemia is 68, and over 75% of new cases occur in people 55 or older. Only about 7.7% of leukemia diagnoses happen in people under 20.
Importantly, these cancer-initiating mutations must occur in stem cells, not in mature blood cells. When researchers introduced cancer-driving mutations into stem cells in animal models, the cells reliably became malignant. The same mutations introduced into non-stem cells did not. This is because stem cells live long enough and divide often enough to accumulate the multiple genetic hits needed to trigger cancer. In some leukemia patients, doctors can find the earliest mutated stem cells still present in the bone marrow even after treatment has eliminated the cancer itself, evidence that the roots of the disease trace back to these long-lived cells.
Chemical Exposures, Especially Benzene
Benzene is the best-established chemical cause of blood cancer. The International Agency for Research on Cancer classifies it as carcinogenic to humans, with the strongest link to acute myeloid leukemia (AML). It may also increase the risk of acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin lymphoma.
Benzene is an organic solvent used in the production of fibers, rubbers, pesticides, paints, adhesives, and gasoline. Workers in the chemical industry, gas station employees, printers, steelworkers, shoemakers, firefighters, and lab technicians can all face occupational exposure. One study found an 11-fold increase in AML risk from cumulative benzene exposures well below 1 part per million per year, a level once considered relatively safe. Benzene’s breakdown products damage DNA in bone marrow cells and impair the cells’ ability to repair that damage, directly feeding the mutation-accumulation process described above.
Tobacco Smoke and Bone Marrow Damage
Smoking is a recognized cause of myeloid leukemia. The 2004 U.S. Surgeon General’s Report formally added it to the list of smoking-related cancers. One reason is straightforward: tobacco smoke contains benzene. But other chemicals in cigarette smoke likely contribute as well. Benzene metabolites damage DNA in the blood-forming cells of the bone marrow while simultaneously weakening those cells’ repair machinery. For people who develop AML, smoking also appears to worsen outcomes by impairing the bone marrow’s ability to recover after treatment.
Radiation Exposure
Ionizing radiation, the type produced by nuclear reactions, X-rays, and radioactive materials, is a well-documented cause of blood cancer. A large international study of nuclear workers in France, the United Kingdom, and the United States found that the leukemia death rate increased by more than 250% per gray of radiation absorbed. (A gray is a standard unit measuring the energy deposited by radiation in body tissue.) The dose-response relationship was essentially linear: more radiation exposure meant proportionally more risk.
The average cumulative dose among workers in the study was quite low at 0.016 gray, yet even at that level the researchers estimated 13 excess leukemia deaths per 100,000 workers over 35 years. These findings closely match data from Japanese atomic bomb survivors, reinforcing that there’s no clearly “safe” threshold for radiation-induced blood cancer.
Viruses That Trigger Blood Cancers
A handful of viruses directly cause or significantly raise the risk of specific blood cancers. Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia, a rare but aggressive cancer found most often in regions where the virus is endemic, including parts of Japan, the Caribbean, and sub-Saharan Africa. Epstein-Barr virus (EBV), the virus behind mononucleosis, is associated with Burkitt’s lymphoma, Hodgkin lymphoma, and lymphomas in people with weakened immune systems. Hepatitis C virus infection has also been linked to a higher incidence of lymphoma, likely through chronic stimulation of immune cells that eventually accumulate dangerous mutations.
Immune System Disruption
Your immune system normally identifies and destroys abnormal cells before they can multiply into a tumor. When this surveillance system breaks down, blood cancers can take hold. Autoimmune diseases, in which the immune system attacks healthy tissue, create a state of chronic inflammation that reshapes the immune environment. Prolonged inflammation drives certain immune cells to divide more rapidly, increasing the opportunity for mutations, while simultaneously training other immune cells to become tolerant of abnormal growth.
Specific cell types play a role in this process. Regulatory immune cells that normally keep inflammation in check can be co-opted by cancer cells to suppress the body’s anti-cancer defenses. This creates a feedback loop where the immune system becomes increasingly blind to malignant cells. The gut microbiome also influences this balance, with its metabolic products either supporting or undermining the immune system’s ability to detect cancer.
Prior Cancer Treatment
Chemotherapy and radiation therapy used to treat one cancer can themselves cause blood cancer years later. These “therapy-related” cases arise because the same treatments that kill cancer cells also damage the DNA of healthy bone marrow stem cells. According to National Cancer Institute data, the cumulative risk of developing therapy-related leukemia or a related bone marrow disorder is less than 1% at 10 years after chemotherapy for most solid tumors. The risk is small in absolute terms but meaningful, since these secondary cancers tend to be harder to treat than blood cancers that arise on their own.
Obesity and Body Weight
Carrying excess weight is an underappreciated risk factor for blood cancer, particularly multiple myeloma. A study in the British Journal of Cancer found an 18% increase in myeloma risk for every 5-point rise in BMI. People with severe obesity (BMI of 40 or higher) had nearly double the risk compared to those at a normal weight. The association was especially strong in Black men, who already face a higher baseline risk of myeloma. Excess body fat promotes chronic low-grade inflammation and alters hormone levels, both of which can create a more hospitable environment for cancer to develop.
Why Age Is the Biggest Risk Factor
More than any single exposure, aging itself is what drives most blood cancers. Every year of life means another year of cell divisions, another year of accumulated mutations, and another year of declining immune surveillance. Leukemia is most frequently diagnosed in people aged 65 to 74, and nearly 58% of all new cases occur in people over 64. While leukemia is among the most common childhood cancers, children account for fewer than 8% of all cases. The biological reality is that time is the main ingredient: the longer your stem cells divide, the more chances they have to acquire the handful of mutations needed to become malignant.