Acute Lymphoblastic Leukemia Pathophysiology

By Dr Ananya Mandal, MD

Acute lymphoblastic leukemia or ALL is the cancer of the lymphoid white blood cells. There are several risk factors that raise the risk of this cancer. However, the exact cause of this cancer is not yet known.

Risk factors for ALL

Some of the risk factors that may be associated with the causation of ALL include:-

Exposure to radiation

Exposure to high levels of radiation is a known risk factor for ALL as well as acute myeloid leukemia (AML).

This was first noted among the Japanese atomic bomb survivors who had a greatly increased risk of getting acute leukemia, usually within 6 to 8 years after exposure.

Radiation may arise from radiation therapy for cancers, radiation from imaging studies like X rays and CT scans etc. Exposure of an unborn baby to radiation within the first months of development may also raise the risk of acute leukemia.

Exposure to chemicals

The risk of ALL may be raised if there in exposure to certain chemotherapy drugs as well as toxins and agents in the environment like benzene.

Benzene is used as a solvent in several industries like rubber, chemical plants, shoe manufacturing, oil refineries, gasoline-related industries etc. It is also present in glues, cleaning products, detergents, paints and cigarette smoke.

Exposure to toxins is strongly related to getting ALL and other acute leukemia.

Viral infections

Some viruses have been implicated in causing leukemia. Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) for example can cause a rare type of T-cell acute lymphocytic leukemia.

Most of these cases occur in Japan and the Caribbean areas – it is not common in the United States.

Further Epstein-Barr virus (EBV) causes mononucleosis and may be linked to Burkitt lymphoma and a form of ALL.

Genetics

ALL is usually not an inherited cancer. The condition does not usually run in families. However, some genetic conditions that do run in families have been associated with ALL. These include Down syndrome, Klinefelter syndrome, Fanconi’s anemia, Ataxia-telangiectasia, Bloom syndrome, Neurofibromatosis etc.

Gender

ALL is slightly more common in males than in females.

Ethnicity and race

ALL is seen more commonly among Caucasians than in African Americans.

Unproven risk factors

Other unproven risk factors include exposure to electromagnetic fields like living near power grids and cell phone towers etc, exposure to pesticides, and certain other chemicals, hair dyes and bleaches and cigarette smoke.

Cause and pathology of ALL

Cancer is usually caused if there is an alteration or mutation of a DNA. The changes in the DNA can cause normal bone marrow cells to become leukemia cells.

There are presence of normal genes that help cells to grow. These are called Oncogenes. Yet other types of genes that slow growth of cells are called tumor suppressor genes. These tumor suppressor genes slow down cell growth and division or cause them to die at appropriate times. Cancer occurs when this balance between Oncogenes and tumor suppressor genes is altered.

Types of DNA error

Common errors seen in DNA are called mutations. Translocations are the most common type of DNA change that form the basis of leukemia. A translocation means that DNA from one chromosome breaks off and becomes attached to another chromosome. This break off at a chromosome can turn on oncogenes or turn off tumor suppressor genes leading to cancers.

The most common translocation in ALL in adults is known as the Philadelphia chromosome, which is a switch of DNA between chromosomes 9 and 22, abbreviated as t(9;22). This is seen in around 25% of all cases of ALL in adults.

Other, less common translocations are those between chromosomes 4 and 11, abbreviated as t(4;11), or 8 and 14, abbreviated as t(8;14).  For example about 25% of cases of B-cell precursor ALL (the most frequent form of acute leukaemia in children) harbour the TEL-AML1fusion gene that is generated by the t(12;21)(p13;q22) chromosomal translocation.

There may be other types of mutations as well. There may deletions where part of a chromosome is lost or inversion where a segment is rearranged and placed wrongly.

In many cases of ALL, the gene changes that lead to the leukemia are not known. Cytogenetic tests help in detection of the genetic mutations. Some mutations carry a good prognosis while some predict a bad outlook for the disease.

The cells implicated in ALL have clonal rearrangements in their immunoglobulin or T-cell receptor genes and express antigen-receptor molecules and cell-surface glycoproteins.

Reviewed by , BA Hons (Cantab)

Further Reading

Last Updated: Feb 26, 2013

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