Leukaemia Flashcards

1
Q

What is the most common cancer in the 15-24 age group?

A

Cancers of the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the literal meaning of leukaemia?

A

White blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where does the problem exist in leukaemia?

A

In the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does leukaemia result from?

A

A series of mutations in a single lymphoid or myeloid stem cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the consequences to the progeny of the mutated cell?

A

These mutations lead to progeny of that cell to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukaemic clone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which cells can be affected in leukaemia?

A
Pluripotent haematopoietic stem cell 
Myeloid stem cell  
Lymphoid stem cell  
Pre B lymphocyte  
Pro T lymphocyte
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the equivalent terms for ‘benign’ and ‘malignant’ in terms of leukaemia?

A

Leukaemias that behave relatively benignly are CHRONIC

Leukaemias that behave in a malignant manner are ACUTE– the disease is very aggressive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the four main types of leukaemia?

A

Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Explain the significance of the terms acute lymphoblastic leukaemia and chronic lymphocytic leukaemia.

A

In ALL the cells are immature – they are lymphoblasts

IN CLL the cells are mature lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the important leukaemogenic mutations that have been recognised?

A

Mutation in a known proto-oncogene
Creation of a novel gene e.g. chimeric or fusion gene
Dysregulation of a gene when translocation brings it under the influence of a promoter or enhancer of another gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

State some inherited or other constitutional abnormalities that can contribute to leukaemogenesis.

A

Down syndrome
Chromosomal fragility syndromes where breaks are common
Defects in DNA repair
Inherited defects in tumour suppressor genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some identifiable causes of leukaemogenic mutations?

A

Irradiation
Anti-cancer drug
Cigarette smoking
Chemicals e.g. benzene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What type of cell is seen in abundance in acute myeloid leukaemia?

A

Immature myeloid cells – the cells continue to proliferate but they no longer mature so there is a build up of immature cells (myeloblasts) in the bone marrow, which spread to the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Explain how acute leukaemia leads to bone marrow failure.

A

The leukaemic cells crowd out the normal cells in the bone marrow leading to a decrease in the production of other end cells e.g. neutrophils, monocytes, platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What do the responsible mutations normally affect in AML?

A

Transcription factors – the transcription of multiple genes is affected
Often the product of an oncogene prevents the normal function of the protein encoded by its normal homologue
This leads to changes in cell kinetics and cell functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What do the responsible mutations normally affect in CML?

A

A gene encoding a protein in the signalling pathway between a cell surface receptor and the nucleus
The protein encoded may be a membrane receptor or a cytoplasmic protein

17
Q

Describe the nature of the leukaemic cells in CML.

A

These are mature lymphocytes – their cell kinetics and function are not as seriously affected as they are in AML but the cells do become independent of external signals, there are alterations in the interaction with stroma and there is reduced apoptosis so that cells survive longer and the leukaemic clone expands progressively

18
Q

How is the production of end cells affected in AML and CML?

A

AML – decrease in the production of end cells. Is increased proliferation but no more maturation
CML – increase in the production of end cells

19
Q

What are the clinical signs of leukaemic cell proliferation?

A
Hyperuricaemia  
Renal failure  
Weight loss  
Low grade fever  
Sweating
20
Q

Which type of leukaemia increases the risk of intraventricular haemorrhage and why?

A

Acute promyelocytic leukaemia (APML) – this is associated with DIC so the platelet count and fibrinogen are low leading to increased risk of fatal haemorrhage

21
Q

How can leukaemia cause proliferation of the gums?

A

Infiltration of leukaemic cells and monocytes can lead to inflammation of the gums
There will be small haemorrhages due to thrombocytopenia

22
Q

What are some factors that relate to risk of leukaemia?

A

Family size, new towns, socio-economic class, early social interactions

23
Q

What can leukaemias in infants and young children result from?

A

Irradiation in utero

In utero exposure to certain chemicals

24
Q

What are the clinical features of acute lymphoblastic leukaemia?

A
Bone pain  
Hepatomegaly  
Splenomegaly  
Lymphadenopathy 
Thymic enlargement  
Testicular enlargement  
These all result from the accumulation of abnormal cells
25
Q

What are some clinical features of acute lymphoblastic leukaemia that result from the crowding out of normal cells

A

Caused by anaemia – fatigue, lethargy, pallor, breathlessness
Caused by neutropenia – fever and other features of infection
Caused by thrombocytopenia – bruising, petechiae, bleeding

26
Q

What investigations are performed in acute lymphoblastic leukaemia?

A
Blood count and film  
Check of liver function and renal function and uric acid  
Bone marrow aspirate  
Cytogenetic/molecular analysis  
Chest X-ray
27
Q

What are the uses of cytogenetic and molecular genetic analysis in ALL?

A

It is useful for managing the individual patient because it gives us information about prognosis
It permits the discovery of leukaemogenic mechanisms

28
Q

What are the implications of hyperdiploidy in in the cytogenetic analysis of ALL?

A

Good prognosis

29
Q

What features of the cytogenetic analysis for ALL are associated with a poor prognosis?

A

Chromosomal translocations resulting in the formation of a bad fusion gene

30
Q

What translocation causes ALL? State the fusion gene.

A

Translocation between chromosome 12 and chromosome 21

Fusion gene: ETV6-RUNX1 on chromosome 12

31
Q

What technique is used to detect the fusion genes in ALL?

A

Fluorescence in situ hybridisation (FISH)

32
Q

What are the treatment options for ALL?

A

Supportive: red cells, platelets, antibiotics
Systemic chemotherapy
Intrathecal chemotherapy

33
Q

What is different about leukemia that separates it from most other cancers?

A

Leukemia doesnt form a tumour instead there is circulation of ‘leukemic’ cells
These cancerous cells migrate around the body whereas in other cancers you wouldnt have an epithelial cell migrating around the body
Concepts of invasion and metastasis cant be applied to cells which normally do enter cells
Concepts of benign and malignant cancers have different ways of being classified

34
Q

Classification of leukemia

A

Acute or chronic
Lymphoid or myeloid lineage
Lymphoid could be T or B lineage
Myeloid can be further classified depending on type of cell

35
Q

Classifications of myeloid leukemias

A

Granulocytic
Monocytic
Erythroid
Megakaryocytic