Introduction to Leukaemias Flashcards
What is leukaemia?
A malignant disorder of haemopoietic cells which involves high numbers of white blood cells in the bone marrow or the peripheral blood
What are haemopoietic cells?
Pluripotent cells which give rise to cells of every blood lineage, they are self-maintaing so they can divide to form more haemopoietic cells
What is haemopoiesis?
Formation of blood cells
What are the three lineages of blood cells?
- Erythrocytes = carries oxygen
- Lymphoid = forms T and B cells for immune response
- Myeloid = innate and blood is clotting
What are progenitor cells? Undifferentiated and Committed
Cells after haemopoietic cells and therefore can divide to produce mature cells but cannot divide indefinitely.
They can be multipotent (cannot differentiate between them morphologically) or they can be committed (know what mature cell they will become and can differentiate)
What are the features of leukaemia?
- Described as being a clonal disease where all the malignant cells derive from one mutant stem cells like haemopoietic or progenitor
How is leukaemia diagnosed?
- The patient will present with symptoms due to abnormal cell proliferation such as bruising, infection and anaemia.
- To diagnose it molecular and pathophysiological tests can be done, such as cytomorphology, immunophenotyping, NGS, FISH and flow cytometry.
What is the aetiology of leukaemia?
- Due to a combination of genetic predisposition, lifestyle factors, environmental factors and uncertain factors.
- The cells will aquire a mutation which convert to stem cells with self-renewal ability. This will cause a pre-leukaemia status but no cancer. Later on, there is a second aquisition of a mutation that produces a full blown leukaemia.
What is the genetic predisposition that can cause leukaemia?
- Not usually hereditary but only in chronic lymphocytic leukaemia
- Some diseases can be predisposing such as Fanconi’s anaemia and Down’s syndrome.
- It is typically caused by a mutation in the oncogen leading to abnormal proliferation or it can be caused by a mutation in the tumour suppressor gene leading to inactivation of apoptosis.
- Involving genes common to other malignancies (TP53- Li-Fraumeni syndrome, NF1-neurofibromatosis) or specific to leukaemia
- Sometimes can also be caused by chromosomal aberration such as CMR-AML and numerical disorders, and finally can be caused by immune system problems such as Ataxia-telangiectasia and Wiskott-Aldrich syndrome.
What is the environmental factors that can cause leukaemia?
- Radiation exposure: acute radiation accidents and atomic bomb survivors e.g. japanese bomb
- Chemotherapy exposure and exposure to chemicals: cancer chemotherapy with alkylating agents e.g. Busulphan and industrial exposure to benzene
- Immune system suppression: Organ transplant
What is the lifestyle factors that can cause leukaemia for some adult cancers?
- Smoking
- Drinking
- Exposure to the sun
- Overweight
What are the first symptoms of leukaemia?
Due to normal blood cell production:
- Abnormal bruising-commonest
- Repeating abnormal infection due to a defect on production of blood cells
- Sometimes anaemia
What are the other possible link to childhood leukaemia?
- Exposure to electromagnetic fields
- Infections early in life
- Mother’s age when child is born
- Nuclear power stations
- Parent’s smoking history
- Foetal exposure to hormones
How are leukaemias classifed?
- Lymphoid or myeloid depending on the lineage
- Acute or chronic: acute is a rapid, severe onset of disease which is undifferentiated leukaemia and characterised by high levels of immature WBC. Chronic is persisting over time, differentiated leukaemia and characterised high levels of mature WBC.
What are the main features of acute leukaemia?
- Occurs in children
- Has a sudden onset of symptoms which lasts around weeks or months and the WBC is variable
- 2 types: acute lymphoblastic leukaemia (ALL) and acute myeloblastic leukaemia (AML)
- Both have altered white cell cycle, where the blast cell pool formation occurs at abnormally high levels and no maturation or senescence of cells occurs
- Leads to symptoms such as thrombocytopenia, purpura, epistaxis, bleeding from gums to occur, recurrent infections due to neutropenia and anaemia
- Diagnosis done via peripheral blood blast test to check for the presence of blasts that should usually be 30%; bone marrow biopsy from the pelvic bone and lumbar puncture to check if the leukaemia has spread to the cerebral spinal fluid
- AML affects cells such as Basophils, Neutrophils, Eosinophils, Monocytes, Macrophages, Erythrocytes and Platelets
- ALL affects cells such as B cells and T cells
