Introduction To Leukaemia Flashcards
Define Leukaemia
A clonal disease where all the malignant cells derive from a signal mutant stem cell
What are haematopoeitic stem cells (HSCs)?
Multi-potent - can give rise to cells of every blood lineage
Self maintaining - a stem cell can divide to produce more stem cells
What are progenitor cells?
Can divide to produce many mature cells
But cannot divide indefinitely
Eventually differentiate and mature
What are undifferentiated (Multipotent) progenitor cells?
You cannot tell the difference between them and differentiated cells morphologically because they do not show characteristics of mature cells
What are committed progenitor cells (unipotent)?
Already committed as to what they will become when they generate mature cells
What are the first symptoms present in leukaemia?
Abnormal bruising commonest
Repeating abnormal infection
Sometimes anaemia
- caused by loss of normal blood cell production
How is leukaemia diagnosed?
Peripheral blood blast test (PB)
- to check for present of blast and cyopeinia.
- >30% blasts are suspected of acute leukaemia
Bone marrow test/biopsy (BM):
- taken from pelvic bone and results compared with PB.
Lumbar puncture:
- to determine if the leukaemia has spread to the cerebral spinal fluid (CSF)
How is leukaemia characterised molecularly and pathophysiologically?
Cytomorphology
Immunophenotyping
Next generation sequencing (NGS)
Flow cytometry
Fluorescence in situ hybridisation (FISH)
What is the aetiology (cause) of leukaemia?
Exact cause if unclear but thought to be a combination of predisposing factors
Genetic risk + environmental factors
Describe the genetic risk factors of leukaemia
NOT usually hereditary (except for some cases of chronic lymphocytic leukaemia (CLL)
Some rare genetic diseases may predispose to leukaemia (eg. Down syndrome)
Gene mutations involving oncogene activation or/and tumour suppressor deactivation (could involve genes common to other malignancies or specific to leukaemia)
Chromosome aberrations (translocations or numerical chromosomal disorders)
Inherited immune system problems (eg. Ataxia)
Describe the environmental risk factors of leukaemia.
Radiation exposure
- acute radiation accidents
- atomic bomb survivors
Exposure to chemicals and chemotherapy
- cancer chemotherapy with alkylating agents
- industrial exposure to benzene
Immune system suppression
- after organ transplant
Describe the lifestyle related risk factors of leukaemia in adults
Smoking
Drinking
Excessive exposure to sun
Overweight
Describe the controversial risk factors of childhood leukaemia
Exposure to electromagnetic fields
Infections early in life
Mothers age when child is born
Nuclear power stations
Parents smoking history
Foetal exposure to hormones
What are the 2 types of acute leukaemia?
Acute lymphoid leukaemia (ALL)
Acute myeloid leukaemia (AML)
What are the 2 types of chronic leukaemia?
Chronic lymphoid leukaemia (CLL)
Chronic Myeloid Leukaemia (CML)
What is a acute disease?
Rapid onset and short but serevre course
What is acute leukaemia?
Undifferentiated leukaemia
Characterised by uncontrolled clonal and accumulation of immature white blood cells (myoblast and lymphoblast) in bone marrow and blood.
What is chronic leukaemia?
Differentiated leukaemia
Characterised by uncontrolled clonal accumulation of mature white blood cells (-cyte)
How is a patient with acute leukaemia classified?
Age is Mainly children
Sudden onset
Duration of weeks to months
WBC count variable
How is a patient with chronic leukaemia classified?
Age is middle aged and elderly
Onset insidious
Duration is years
WBC count is high
What are the typical symptoms of acute leukaemia?
Due to bone marrow suppression
Thrombocytopenia - purpura (bruising), epistaxis (nosebleed), bleeding from gums
Neutropenia - recurrent infections, fever
Anaemia: lassitude, weakness, tiredness, shortness of breath
What is acute lymphoblastic leukaemia (ALL)?
Prevalence: Commonest cancer of childhood
Origin: cancer of immature lymphocytes
Classification: B cell and T cell leukaemia
Treatment: chemotherapy. Long term side effects are rare
Outcome: 1/10 of ALL patients relapse. Remission is 50% after the second chemotherapy treatment or bone marrow transplant.
What is acute myeloblastic leukaemia (AML)?
Prevalence: 70 children < 16 years old diagnosed every year in the UK. (Very rare)
Origin: cancer of immature myeloid white blood cells
Classification: based on FAB system (French American British)
Treatment: chemotherapy, monoclonal antibodies, allogenic bone marrow transplant.
Outcome: 5 year event-free survival (EFS) of 50-60%
What is chronic lymphocytic leukaemia?
Prevalence: 3800 new cases in uk every year
Origin: large numbers of mature lymphocytes in bone marrow and peripheral blood
Symptoms: recurrent infections due to neutropenia, and suppression of normal lymphocyte function, anaemia, lymph node enlargement, hepatosplenomegaly
Treatment: Regular chemotherapy to reduce cell numbers
Outcome: 5 year event free survival (EFS) of 83%. Many patients survive > 12 years. 
