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MBD > Introduction To Leukaemia > Flashcards

Introduction To Leukaemia Flashcards

1
Q

Define leukaemia

A

Malignant disorders of haematopoetic stem cells characteristically associated with an increase number of white cells in bone marrow or land peripheral blood

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2
Q

What are haematopoeitic stem cells?

A

Multipotent and self-maintaining

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3
Q

What can progenitor cells divide to produce?

A

Many mature cells

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4
Q

Name the 2 possible progenitors that an HSC can become - can these self renew?

A
  • Common myeloid progenitor
  • Common lymphoid progenitor

These can divide to produce many mature cells but cannot divide indefinitely like HSCs

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5
Q

What are the two types of progenitor cells?

A

Undifferentiated and committed

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6
Q

What is a clonal disease?

A

When all malignant cells derive from a single mutant cell

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7
Q

In which of the cells might a mutation occur in leukaemia?

A

In an HSC or a progenitor (I believe this has to be a multipotent progenitor)

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8
Q

Explain what property the mutation must give the cell to achieve a ‘pre-leukaemic’ state

A

Self-renewal

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9
Q

Explain what properties the secondary mutations must give the cell to become a full blow leukaemia stem cell

A

Increased survival and proliferation (as well as the self renewal properties from the first mutation)

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10
Q

Describe the incidence of leukaemia

A
  • 3% of total cancer cases
  • 85-89 is when you are most likely to get it
  • more common in men than women
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11
Q

Describe the presentation (generally) of leukaemia

A

Is usually detected due to symptoms from the loss of normal blood cell production so:

  • abnormal bruising (low platelets?)
  • repeating abnormal infection (low WBCs?)
  • sometimes anaemic
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12
Q

Name a blood test that we can do to diagnose leukaemia

A
  • Peripheral blood blast
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13
Q

Other than a Peripheral blood blast test what else can you use to diagnose leukaemia?

A
  • Bone marrow biopsy
  • Lumbar puncture
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14
Q

What does a peripheral blood blast test in the diagnosis of leukaemia?

A

To check the presence of blasts and cytopenia

  • If there is more than 30% blasts then acute leukaemia is suspected
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15
Q

Where is the bone marrow biopsy taken from?

A

Pelvic bone and results compared with peripheral blood

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16
Q

Why is a lumbar puncture done?

A

To determine if leukaemia has spread to the CSF

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17
Q

What are the possible predisposing factors for leukaemia?

A
  • Genetic risk factors
  • Environmental risk factors
  • Lifestyle-related risk factors
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18
Q

What syndromes increase the likelihood of leukaemia?

A

Downs and fanconi’s anaemia

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19
Q

What are the genetic risk factors for leukaemia?

A
  • Gene mutations involving oncogenes and/or tumour suppressors
  • Chromosome aberrations
  • Inherited immune system problems
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20
Q

What types of chromosomal abberations increase the risk for leukaemia?

A
  • Translocations
  • Numerical disorders
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21
Q

Describe the role of the Philadelphia chromosome in genetic risk of leukaemia

A
  • Is a chromosomal translocation leading to the BCR and ABL genes being put together.
  • Accounts for 95% of the cases of CML (chronic myeloid luekaemia)
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22
Q

Describe the role of numerical chromosomal disorders in risk of leukaemia

A

All of them increase risk

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23
Q

Name another type of illness that may cause increased risk to Leukaemia

A

Immune system problems such as ataxia telengiectasia or Wiskott-Aldrich syndrome)

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24
Q

What are the environmental risk factors for leukaemia?

A
  • Radiation exposure
  • Exposure to chemicals and chemo
  • Immune system suppression
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25
What type of radiation exposure is a risk factor for leukaemia?
* Acute radiation accidents * Atomic bomb survivors
26
What type of exposure to chemicals and chemo is a risk factor for leukaemia?
* Cancer chemo with alkylating agents * Industrial exposure to benzene
27
What lifestyle risk factors are there for leukaemia?
* Smoking * Drinking * Excessive sun exposure * Overweight
28
What are the risk factors for childhood leukaemia?
* Exposure to EM fields * Infections early in life * Mothers age when the child is born * Nuclear power stations * Parents smoking history * Foetal exposure to hormone
29
What are the four main types of leukaemia?
* Acute lymphoblastic leukaemia (ALL) * Acute myeloblastic leukaemia (AML) * Chronic lymphocytic leukaemia (CLL) * Chronic granulocytic leukaemia (CML)
30
What are the features of acute disease (in general)?
Rapid onset and short but severe course
31
What are the features of chronic disease (in general)?
Persisting over a long time
32
Explain what is meant by acute leukaemia
Characterised by uncontrolled clonal accumulation of blast WBCs (either myeloblast or lymphoblast) which are undifferentiated * short onset and severe symptoms
33
Explain what is meant by chronic leukaemia
* Persisting over a long time * This is differentiated leukaemia as it is characterised by uncontrolled accumulation of mature WBCs (-cytes instead of -blasts)
34
What is the normal age of onset of acute leukaemia?
Childhood
35
What is the normal style of onset of acute leukaemia?
Sudden
36
What is the normal duration of acute leukaemia?
Weeks to months
37
What is the normal white blood cell count in acute leukaemia?
Variable
38
What is the normal age of onset of chronic leukaemia?
Middle age and elderly
39
What is the normal style of onset of chronic leukaemia?
Insidious
40
What is the normal duration of chronic leukaemia?
Years
41
What is the normal white blood cell count in chronic leukaemia?
High
42
Acute leukaemia is the commonest type of cancer in which age group?
Childhood (31%)
43
What is more common, ALL or AML?
* 75% of childhood cancer cases are ALL * 20% are AML
44
What is ALL characterised by?
Large number of lymphoblasts
45
What is AML characterised by?
Large number of myeloblasts
46
Describe how the mature cell numbers are affected in acute leukaemia
There is inhibition of the maturation of the blast cells as well as increased replication - so they accumulate
47
What are the typical lab symptoms of ALL/AML?
* Thrombocytopenia * Neutropenia * Anaemia
48
What is thrombocytopenia?
Low platelet count
49
What are the clinical symptoms of thrombocytopenia?
* Purpura (bruising) * Epistaxis (nosebleed) * Bleeding from gums
50
What are the clinical features of neutropenia?
Recurrent infections and fever
51
What are the clinical symptoms of anaemia?
* Weakness * Tiredness * Shortness of breath
52
What are the skin symptoms of leukaemia?
* Night sweats * Easy bleeding and bruising * Purplish patches or spots
53
What are the bone symptoms of leukaemia?
Pain or tenderness
54
What are the resp symptoms of leukaemia?
Easy shortness of breath
55
What are the systemic symptoms of leukaemia?
* Weight loss * Fever * Frequent infections
56
Describe the outcome (survival) of ALL
* 1 out of 10 patients relapse but if you don’t then there is a survival (event free survival) of 87% for 5 years. * In adults, ALL (less frequent) is more difficult to treat.
57
How do you treat ALL?
Chemo
58
How is AML classified?
M0-M7
59
Describe the rarity of AML
Less than 70 children a year so is very rare
60
How do you treat AML?
* Chemo, immunotherapy * With/without allogenic bone marrow transplant
61
Describe a risk of acute leukaemia treatment
Patients are immunocompromised due to the disease but also due to the chemotherapy and so they are prone to infections - need to be given antibiotics if they have a fever
62
What is chronic leukaemia characterised by?
Increased number of differentiated cells
63
Describe the prevalence and onset of chronic leukaemias as opposed to acute
More common and later onset
64
What is the average age of CLL onset?
70
65
What is CLL characterised by?
Large number of mature lymphocytes in bone marrow and peripheral blood
66
As well as the normal leukaemia symptoms, describe the other symptoms of CLL
* lymph node enlargement * liver and spleen swelling (hepatosplenomegaly)
67
What is the treatment and prognosis for CLL?
EFS of 83% (good especially as average age is 70) * treatment is chemotherapy
68
Is CLL or CML more common?
CLL
69
Describe the age of onset for CML as well as its symptoms
85-89 Often asymptomatic
70
How is CML usually discovered?
Routine blood tests
71
What are the hallmarks of CML in the blood?
Very high white cell count (neutrophilia) and the presence of Philadelphia chromosome
72
What is CML treated by?
Imatinib
73
What does the BCR gene encode?
A protein that needs to be continually active
74
What does the ABL gene encode?
tyrosine kinase
75
What does unregulated BCR-ABL cause?
* Proliferation of progenitor cells in the absence of growth factors * Decreased apoptosis * Decreased adhesion to bone marrow
76
Explain how we use Imatinib and how it works
This is a CML targeted therapy and it inhibits BCR-ABL * small molecule inhibitor that stops ATP from binding to the tyrosine kinase (?) so that targets can not be phosphorylated
77
Which two chromosomes is the Philadelphia made of - which two genes are put in close contact also?
made of chromosome 9 long arm and 22 long arm - brings together the chromosomes 9 and 22
78
Describe the effects of the Philadelphia chromosome on bone marrow cells
* proliferation of progenitor cells in the absence of growth factors * decreased apoptosis * decreased adhesion to bone marrow stroma So, causes CML
79
How can we use the fact that most CML cases have a Philadelphia chromosome clinically?
* For diagnosis of CML. * But also for detection of minimal residual disease by looking for the Philadelphia chromosome (only in the cancerous CML cells).

MBD (23 decks)

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