Introduction to Leukaemia Flashcards
(36 cards)
What are the three major blood cancers?
- Leukaemia
- Lymphoma
- Myeloma
What is Leukaemia?
Malignant disorder of the haematopoietic stem cells associated with increased white blood cells in bone marrow and peripheral blood
What are the features of haematopoietic stem cells?
- Pluripotent = Give rise to blood cells of every lineage
- Self-Maintaining = A stem cell that can divide and produce more stem cells
What are the features of progenitor cells?
- Can divide to produce many mature cells
- Can be multipotent/unipotent
- Eventually differentiate and mature
- But cannot divide indefinitely!!!
What are the two types of progenitor cells?
Undifferentiated (Multipotent) = Have the ability to form different types of blood cells Committed (Unipotent) = Committed to a particular cell line and produce one type of blood cell
What does it mean by saying Leukaemia is a clonal disease?
All malignant cells derive from a mutation in a single stem cell (either a mutation in the haematopoeitic stem cell or a progenitor cell)
- Mutation converts cell into stem cell with self-renewal abillity
- = causes the pre-leukaemia status
- During development in individuals life acquisition of another/second mutation is necessary to give rise to full-blown leukaemia
- = causes abnormal levels of proliferation + cell survival producing a leukaemia state
What are the general symptoms of leukaemia that you first present?
Will vary depending on the type of leukaemia but typically first you will present with symptoms due to loss of normal blood cell production
- Abnormal bruising (thrombocytopenia, epistaxis (nose bleed) and bleeding from gums
- Repeating abnormal infection (Neutropenia, fevers)
- Sometimes anaemia (this is because the bone marrow is overproducing white cells and there is little room for normal RBC’s to develop)
What is the aetiology of leukaemia?
- Exact cause of leukaemia is unclear
- It is a combination of predisposing factors including:
- Genetic risk factors, environmental factors and lifestyle related risk factors (polyetiologic)
Genetic factors of leukaemia
- NOT USUALLY HEREDITARY except for CLL and rare hereditary diseases which may predispose leukaemia like Fanconi’s anaemia + Down’s Syndrome
What can genetic causes of leukaemia be explained by?
-
Genetic mutations involving oncogenes (activation) or/and tumour suppressors (inactivation) lead to leukaemia
- Involving genes common to other malignancies (Tp53-Li-Fraumeni Syndrome, NF-1 Neurofibromastosis) or specific leukaemia
-
Chromosome Aberrations:
- Translocations (e.g BCR-ABL in CML)
- Numerical disorders (e.g trisomy 21-Down Syndrome)
-
Inherited immune system problems
- e.g Ataxia-telangiectasia, Wiskott-Aldrich syndrome)
What are environmental risk factors associated with leukaemia?
-
Radiation exposure
- Acute radiation accidents
- Atomic bomb survivors
-
Exposure to chemicals + chemotherapy
- Cancer chemotherapy with alkylating agents (e.g Busulphan)
- Industrial exposure to benzene
-
Immune system suppression
- E.g After organ transplant
What can leukaemia be split into?
- Acute Lymphoblastic leukaemia (ALL)
- Acute Myeloblastic Leukaemia (AML)
- Chronic Lymphocytic Anaemia (CLL)
- Chronic Granulocytic/Myeloid Leukaemia (CML)
What is the difference between acute and chronic leukaemia?
Acute (undifferentiated) = Characterised by rapid onset and short but severe course, undifferentiated leukaemia, characterised by untrolled clonal accumulation of immature WBC’s known as myeloblasts/lymphoblasts
Chronic (differentiated) = Persists over a long period of time, differentiated leukaemia, characterised by uncontrolled clonal and accumulation of mature (cyte) blood cells
Describe the age onset, duration and wbc count in acute and chronic leukaemia
Describe undifferentiated leukaemia
- Acute leukaemia can also be termed undifferentiated leukaemia
- Characterised by a large number of lymphoblasts (ALL) or myeloblasts (AML) in bone marrow and blood
- In a normal individual pool of blast cells which differentiate and become mature will die via apoptosis and necrosis
- In leukaemia there is an arrest in the blast cell pool, cells are unable to differentiate and there will be a lack of mature cells = cause acute leukaemia
What are the general symptoms of acute leukaemia?
- They are all related to bone marrow suppression
- Thrombocytopenia: purapura (bruising), epitaxis (nosebleed), bleeding from gums Neutropenia: Recurrent infections, fever
- Anaemia: Iassitude, weakeness, tiredness, shortness of breath
How do we diagnose acute leukaemia?
Diagnosis -
- Peripheral blood blasts test (PB) = to check for presence of blasts and cytopenia. >30% blasts are suspected of acute leukaemia
- Bone marrow test/ biopsy (BM) = taken from pelvic bone and results compared with peripheral blood test (to validate presence)
- Lumbar puncture = determines if leukaemia has spread to CSF
Describe Acute Lymphoblastic Leukaemia (ALL)
B and T cell leukaemia
- Cancer of immature lymphocytes (lymphoblasts)
What is the prevalence of acute lymphoblastic leukaemia?
- Commonest childhood cancer (31%)
- But overall still not very common
- Adult ALL (poorer prognosis because disease presents different cell of origin and different oncogene mutations)
How do we treat acute lymphoblastic leukaemia (ALL)?
- Treatment: Chemotherapy. Long term side effects are rare
- Outcome: 5 year event-free survival (EFS) of 87% in 2010. 1 out of 10 ALL patients relapse. Remission in 50% percent of them after second chemotherapy treatment or bone marrow transplant.
What is Acute Myeloblastic Leukaemia (AML)?
What is its prevalence?
Cancer of immature myeloid white blood cells/ myeloblasts
Prevalence = Very rare (70 children aged <16 y/o diagnosed in the UK every year
How do we treat acute myeloblastic leukaemia (AML)?
- Treatment: Chemotherapy, monoclonal antibodies (immunotherapy) +/- allogeneic bone marrow transplant.
- Outcome: 5 year event-free survival (EFS) of 50-60%.
What is Chronic Lymphocytic Leukaemia (CLL)?
Large numbers of mature (clonal) lymphocytes in bone marrow and peripheral blood
Who is most affected by chronic lymphocytic leukaemia (CLL)? And what are the symptoms of it?
- Prevalence = greater association with adults (Average diagnosis aged 70)
- Symptoms
- Thrombocytopenia: purpura, epistaxis, bleeding from gums
- Neutropenia: Recurrent infections, fever
- Anaemia: lassitude, weakness, tiredness, shortness of breath
- Lymph node enlargement
- Hepatosplenomegaly
