“Group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood”.
• These abnormal cells cause symptoms because of:
– Bone marrow failure (e.g. anaemia, neutropenia, thrombocytopenia)
– Infiltration of organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin or testes).
Classification:
The main classification is into four types: acute and chronic leukaemias, which are further subdivided into lymphoid or myeloid.
- Acute leukaemias are usually aggressive diseases in which malignant transformation occurs in the haemopoietic stem cell or early progenitors.
- Genetic damage is believed to involve several key biochemical steps resulting in
– An increased rate of proliferation
– Reduced apoptosis
– A block in cellular differentiation.
Together these events cause accumulation in the bone marrow of early haemopoietic cells known as blast cells. - The dominant clinical feature of acute leukaemia is usually bone marrow failure caused by accumulation of blast cells, although organ infiltration also occurs.
- If untreated, acute leukaemias are usually rapidly fatal, although with modern treatments most younger patients are ultimately cured of their disease.
Causes:
The exact causes of leukemia are not always clear, but several factors have been linked to its development. Here are some of the known causes and risk factors:
Genetic factors: Certain genetic mutations or chromosomal abnormalities can increase the risk of developing leukemia. These mutations may be inherited from parents or acquired during a person’s lifetime.
Exposure to ionizing radiation: High levels of ionizing radiation, such as those experienced during radiation therapy or nuclear accidents, have been associated with an increased risk of leukemia.
Chemical exposure: Prolonged exposure to certain chemicals and toxins, such as benzene, pesticides, and certain chemotherapy drugs, can increase the likelihood of developing leukemia.
Previous cancer treatment: Some cancer treatments, like radiation therapy and certain chemotherapy drugs, can damage the bone marrow and increase the risk of developing leukemia later in life.
Family history: Having a family history of leukemia or other blood disorders can elevate the risk of developing the disease.
Down syndrome: Individuals with Down syndrome have an increased risk of developing leukemia, particularly acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Myelodysplastic syndromes (MDS): MDS are a group of disorders in which the bone marrow does not produce enough healthy blood cells, and they have an increased risk of progressing to leukemia.
Viral infections: In some cases, specific viral infections, such as human T-cell leukemia virus (HTLV-1) and Epstein-Barr virus (EBV), have been associated with certain types of leukemia.
Risk Factors:
The risk factors for leukemia include:
Genetic Predisposition: Certain genetic factors may play a role in the development of leukemia. People with a family history of leukemia or certain genetic disorders like Down syndrome, Li-Fraumeni syndrome, Fanconi anemia, or Bloom syndrome may have a higher risk.
Previous Cancer Treatments: Individuals who have undergone previous cancer treatments such as radiation therapy or chemotherapy are at an increased risk of developing leukemia later in life.
Exposure to Radiation: Prolonged exposure to high levels of ionizing radiation, such as radiation from nuclear accidents or medical radiation, has been linked to an increased risk of leukemia.
Chemical Exposure: Exposure to certain chemicals and toxins, such as benzene, formaldehyde, and some chemotherapy drugs, may increase the risk of leukemia.
Smoking and Tobacco Use: Cigarette smoking has been associated with an increased risk of acute myeloid leukemia (AML).
Age: Leukemia is more commonly diagnosed in older adults, though it can occur at any age, including in children.
Gender: Some types of leukemia are more common in men (e.g., chronic lymphocytic leukemia) or women (e.g., acute promyelocytic leukemia).
Certain Viral Infections: Infection with certain viruses, such as human T-cell leukemia virus (HTLV-1) or Epstein-Barr virus (EBV), has been linked to certain types of leukemia.
Immune System Disorders: Certain immune system disorders, like HIV/AIDS, may increase the risk of developing leukemia.
Family History of Blood Disorders: A family history of certain blood disorders, such as myelodysplastic syndrome (MDS) or aplastic anemia, may be associated with a higher risk of leukemia.
Certain Genetic Mutations: Specific gene mutations, such as the Philadelphia chromosome in chronic myeloid leukemia (CML), are linked to the development of certain types of leukemia.
Diagnosis of acute leukemia:
Acute leukaemia is normally defined as the
“Presence of over 20% of blast cells in the bone marrow at clinical presentation”.
- However, it can be diagnosed with less than 20% blasts if specific leukaemia‐associated cytogenetic or molecular genetic abnormalities are
present. - The lineage of the blast cells is defined by microscopic examination (morphology), immunophenotypic (flow cytometry), cytogenetic and molecular analysis.
- This will define whether the blasts are of myeloid or lymphoid lineage and also localize the stage of cellular differentiation.
- The typical ‘myeloid immunophenotype’ is CD13, CD33+ and TdT−.
- Special antibodies are helpful in the diagnosis of the rare undifferentiated, erythroid or megakaryoblastic subtypes.
- Cytogenetic and molecular analysis is essential and is usually performed on marrow cells, although blood may be used if the blast cell count is particularly high.
- Cytochemistry can be useful in determining the blast cell lineage but is no longer performed in centres where the newer and more definitive tests are available.
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