Leukaemia

Question 1

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

Answer 1

Cancers of the blood

Question 2

What is the literal meaning of leukaemia?

Answer 2

White blood

Question 3

Where does the problem exist in leukaemia?

Answer 3

In the bone marrow (not all patients have abnormal cells in the blood)

Question 4

What does leukaemia result from?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

Which cells can be affected in leukaemia?

Answer 6

Pluripotent haematopoietic stem cell 
Myeloid stem cell  
Lymphoid stem cell  
Pre B lymphocyte  
Pro T lymphocyte

Question 7

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

Answer 7

Leukaemias that behave relatively benignly are CHRONIC

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

Question 8

What are the four main types of leukaemia?

Answer 8

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

Question 9

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

Answer 9

In ALL the cells are immature – they are lymphoblasts

IN CLL the cells are mature lymphocytes

Question 10

What are the important leukaemogenic mutations that have been recognised?

Answer 10

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

Question 11

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

Answer 11

1. Down syndrome
2. Chromosomal fragility syndromes
3. Defects in DNA repair
4. Inherited defects in tumour suppressor genes

Question 12

What are some identifiable causes of leukaemogenic mutations?

Answer 12

1. Irradiation
2. Anti-cancer drug
3. Cigarette smoking
4. Chemicals e.g. benzene

Question 13

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

Answer 13

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

Question 14

Explain how acute leukaemia leads to bone marrow failure.

Answer 14

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

Question 15

What do the responsible mutations normally affect in AML?

Answer 15

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

Question 16

What do the responsible mutations normally affect in CML?

Answer 16

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

Question 17

Describe the nature of the leukaemic cells in CML.

Answer 17

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

Question 18

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

Answer 18

AML – decrease in the production of end cells

CML – increase in the production of end cells

Question 19

What are the metabolic effects of leukaemic cell proliferation?

Answer 19

Hyperuricaemia  
Renal failure  
Weight loss  
Low grade fever  
Sweating

Question 20

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

Answer 20

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

Question 21

How can leukaemia cause proliferation of the gums?

Answer 21

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

Question 22

What does epidemiology suggest that B lineage acute lymphoblastic leukaemia may result from?

Answer 22

It may result from delayed exposure to a common pathogen

Question 23

What are some factors that relate to risk of leukaemia?

Answer 23

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

Question 24

What can leukaemias in infants and young children result from?

Answer 24

Irradiation in utero

In utero exposure to certain chemicals

Question 25

What are the clinical features of acute lymphoblastic leukaemia?

Answer 25

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

Question 26

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

Answer 26

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

Question 27

What investigations are performed in acute lymphoblastic leukaemia?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

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

Answer 29

Good prognosis

Question 30

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

Answer 30

Chromosomal translocations resulting in the formation of a bad fusion gene

Question 31

What translocation causes ALL? State the fusion gene.

Answer 31

Translocation between chromosome 12 and chromosome 21

Fusion gene: ETV6-RUNX1 on chromosome 12

Question 32

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

Answer 32

Fluorescence in situ hybridisation (FISH)

Question 33

What are the treatment options for ALL?

Answer 33

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

Question 34

What % of all cancers are of the blood

Answer 34

5%

- main causes of cancer death in those aged 1-34

Question 35

What would you see on the CT of leukaemia ?

Answer 35

Intraventricular haemorrhage

Question 36

What happens to the function of the immune system in CLL?

Answer 36

loss of normal function

Question 37

At what age is the highest incidence of ALL?

Answer 37

4

largely a disease of children

Question 38

Give some acute lymphoblastic leukaemia—leukaemogenic mechanisms

Answer 38

1. Formation of a fusion gene
2. Dysregulation of a proto-oncogene by juxtaposition of it to the promoter of another gene, e.g. a T-cell receptor gene
3. Point mutation in a proto-oncogene

Question 39

Give an example of dysregulation in ALL

Answer 39

t(10;14)(q24;q11)—the TCL3 gene is dysregulated by proximity to the TCRA gene