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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
Q

What type of radiation exposure is a risk factor for leukaemia?

A
  • Acute radiation accidents
  • Atomic bomb survivors
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26
Q

What type of exposure to chemicals and chemo is a risk factor for leukaemia?

A
  • Cancer chemo with alkylating agents
  • Industrial exposure to benzene
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27
Q

What lifestyle risk factors are there for leukaemia?

A
  • Smoking
  • Drinking
  • Excessive sun exposure
  • Overweight
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28
Q

What are the risk factors for childhood leukaemia?

A
  • 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
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29
Q

What are the four main types of leukaemia?

A
  • Acute lymphoblastic leukaemia (ALL)
  • Acute myeloblastic leukaemia (AML)
  • Chronic lymphocytic leukaemia (CLL)
  • Chronic granulocytic leukaemia (CML)
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30
Q

What are the features of acute disease (in general)?

A

Rapid onset and short but severe course

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31
Q

What are the features of chronic disease (in general)?

A

Persisting over a long time

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32
Q

Explain what is meant by acute leukaemia

A

Characterised by uncontrolled clonal accumulation of blast WBCs (either myeloblast or lymphoblast) which are undifferentiated

  • short onset and severe symptoms
33
Q

Explain what is meant by chronic leukaemia

A
  • Persisting over a long time
  • This is differentiated leukaemia as it is characterised by uncontrolled accumulation of mature WBCs (-cytes instead of -blasts)
34
Q

What is the normal age of onset of acute leukaemia?

A

Childhood

35
Q

What is the normal style of onset of acute leukaemia?

A

Sudden

36
Q

What is the normal duration of acute leukaemia?

A

Weeks to months

37
Q

What is the normal white blood cell count in acute leukaemia?

A

Variable

38
Q

What is the normal age of onset of chronic leukaemia?

A

Middle age and elderly

39
Q

What is the normal style of onset of chronic leukaemia?

A

Insidious

40
Q

What is the normal duration of chronic leukaemia?

A

Years

41
Q

What is the normal white blood cell count in chronic leukaemia?

A

High

42
Q

Acute leukaemia is the commonest type of cancer in which age group?

A

Childhood (31%)

43
Q

What is more common, ALL or AML?

A
  • 75% of childhood cancer cases are ALL
  • 20% are AML
44
Q

What is ALL characterised by?

A

Large number of lymphoblasts

45
Q

What is AML characterised by?

A

Large number of myeloblasts

46
Q

Describe how the mature cell numbers are affected in acute leukaemia

A

There is inhibition of the maturation of the blast cells as well as increased replication - so they accumulate

47
Q

What are the typical lab symptoms of ALL/AML?

A
  • Thrombocytopenia
  • Neutropenia
  • Anaemia
48
Q

What is thrombocytopenia?

A

Low platelet count

49
Q

What are the clinical symptoms of thrombocytopenia?

A
  • Purpura (bruising)
  • Epistaxis (nosebleed)
  • Bleeding from gums
50
Q

What are the clinical features of neutropenia?

A

Recurrent infections and fever

51
Q

What are the clinical symptoms of anaemia?

A
  • Weakness
  • Tiredness
  • Shortness of breath
52
Q

What are the skin symptoms of leukaemia?

A
  • Night sweats
  • Easy bleeding and bruising
  • Purplish patches or spots
53
Q

What are the bone symptoms of leukaemia?

A

Pain or tenderness

54
Q

What are the resp symptoms of leukaemia?

A

Easy shortness of breath

55
Q

What are the systemic symptoms of leukaemia?

A
  • Weight loss
  • Fever
  • Frequent infections
56
Q

Describe the outcome (survival) of ALL

A
  • 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
Q

How do you treat ALL?

A

Chemo

58
Q

How is AML classified?

A

M0-M7

59
Q

Describe the rarity of AML

A

Less than 70 children a year so is very rare

60
Q

How do you treat AML?

A
  • Chemo, immunotherapy
  • With/without allogenic bone marrow transplant
61
Q

Describe a risk of acute leukaemia treatment

A

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
Q

What is chronic leukaemia characterised by?

A

Increased number of differentiated cells

63
Q

Describe the prevalence and onset of chronic leukaemias as opposed to acute

A

More common and later onset

64
Q

What is the average age of CLL onset?

A

70

65
Q

What is CLL characterised by?

A

Large number of mature lymphocytes in bone marrow and peripheral blood

66
Q

As well as the normal leukaemia symptoms, describe the other symptoms of CLL

A
  • lymph node enlargement
  • liver and spleen swelling (hepatosplenomegaly)
67
Q

What is the treatment and prognosis for CLL?

A

EFS of 83% (good especially as average age is 70)

  • treatment is chemotherapy
68
Q

Is CLL or CML more common?

A

CLL

69
Q

Describe the age of onset for CML as well as its symptoms

A

85-89

Often asymptomatic

70
Q

How is CML usually discovered?

A

Routine blood tests

71
Q

What are the hallmarks of CML in the blood?

A

Very high white cell count (neutrophilia) and the presence of Philadelphia chromosome

72
Q

What is CML treated by?

A

Imatinib

73
Q

What does the BCR gene encode?

A

A protein that needs to be continually active

74
Q

What does the ABL gene encode?

A

tyrosine kinase

75
Q

What does unregulated BCR-ABL cause?

A
  • Proliferation of progenitor cells in the absence of growth factors
  • Decreased apoptosis
  • Decreased adhesion to bone marrow
76
Q

Explain how we use Imatinib and how it works

A

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
Q

Which two chromosomes is the Philadelphia made of - which two genes are put in close contact also?

A

made of chromosome 9 long arm and 22 long arm - brings together the chromosomes 9 and 22

78
Q

Describe the effects of the Philadelphia chromosome on bone marrow cells

A
  • proliferation of progenitor cells in the absence of growth factors
  • decreased apoptosis
  • decreased adhesion to bone marrow stroma

So, causes CML

79
Q

How can we use the fact that most CML cases have a Philadelphia chromosome clinically?

A
  • 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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