By Dr Ananya Mandal, MD
How does leukemia develop?
The human body consists of trillions of cells. Each cell contains chromosomes. A gene is the component of chromosomes that carry genetic messages. The gene is made up of a strand of Deoxyribonuclieic acid (DNA). Damage to the DNA is responsible for the initiation of cancer. The damage may be in the form of shifting or rearrangement of chromosomal bits and segments.
Normally the DNA is capable of correcting its damage on its own. When this self-correcting measure fails, cancer develops. Damage to the DNA of white blood cells can lead to onset of leukemia. A single type of leukemia may contain several genetic abnormalities.
Acute Leukemia, especially of the myeloid variety (AML), results from a defect in the proliferation and maturation of white blood cells within the bone marrow. These immature leukocytes fail to develop into mature leukocytes. Leukemia is suspected when there is an excess of immature leukocytes in blood or bone marrow.
Chronic leukemia affects adults more commonly than acute leukemia. They may have a slower progress than acute leukemias. This is the benign phase that is followed by a ‘blast’ phase where the disease progress is vastly accelerated. As in acute leukemia, there may be chromosomal abnormalities in chronic myeloid leukemia (CML).These changes may lead to specific alterations in certain proteins and enzymes in the body. Commonly an enzyme called tyrosine kinase shows increased activity in CML due to the Philadelphia chromosome (a chromosomal abnormality).
Causes and risk Factors
The exact cause of leukemia is unknown but several risk factors may raise the chance of getting leukemias. These include familial and genetic risks as well as environmental and lifestyle factors.
Familial and genetic factors
Genetic abnormalities play an important role only for a small proportion of cases of leukemias. In most of the cases there is an interaction with faulty genes and DNA damage with environmental and lifestyle factors to bring about risk of leukemia.
Some genetic abnormalities have been associated with leukemias directly. These include Philadelphia chromosome and its association with CML. Klinefelter syndrome, Down syndrome, Bloom syndrome ataxia, telangiectasia and Fanconi syndrome are chromosomal disorders leading to predisposition of leukemia.
First-degree relatives including parents, siblings, or direct offspring with chronic leukemia have a two to four times increased risk for this cancer.
Most (70%) of the leukemias are seen in patients over the age of 50. Patients diagnosed with AML, CML and CLL are usually adults and the elderly. ALL, however is more common in early childhood.
It is suggested that the chromosomes of white blood cells of the elderly are fragile and more prone to DNA damage and changes that may lead to leukemia. With age, there is a reduced ability of the DNA to repair itself and protect itself against damage. There could also be free radical damage to the DNA in the elderly.
This includes factors like smoking and dietary factors. A diet rich in fruits and vegetables and other antioxidants can help prevent against DNA damage caused by free radicals and thus may have a role in reducing the risk of call cancers including leukemias. Increased cigarette smoking is associated with increased risk of leukemia. Cigarettes contain agents such as benzene and other chemicals that have been linked to leukemias.
Studies have shown that several environmental and past exposures may raise the risk of leukemias. Previous exposure to chemotherapy and radiation raises the risk of leukemias.
Alkylating agents, used to treat other cancers, significantly increases the risk of leukemia. In patients treated with alkylating agents for various cancers, there is an increased likelihood of development of leukemia.
Ionizing radiation used for other cancers raises risk of AML, ALL, and CML but not for CLL. Those exposed to radiation are also at risk of leukemias. Studies show that half of all cases of leukemia diagnosed between 1950 and 1987 were attributable to radiation in Hiroshima and Nagasaki after the atomic bomb explosion.
Certain chemicals like benzene raise the risk of leukemias. Benzene is used as a solvent in leather, printing and petrochemical industries. Benzene exposure occurs at the workplace or by environmental sources such as tobacco smoking.
Acute leukemia, especially those affecting T cells, may be caused by exposure to the human T cell leukemia virus (HTLV). This virus has proteins that attaches to the proteins in the lymphocytes and causes abnormalities in their growth leading to cancer.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)