Leukaemia Flashcards Preview

MCD: Cancer > Leukaemia > Flashcards

Flashcards in Leukaemia Deck (26)
Loading flashcards...
1
Q

What is leukaemia?

A

Blood cancer.
‘White blood’- first cases recognised had increased white cell count.
Bone marrow disease- not all patients have abnormal cells in blood.

2
Q

What percentage of cancers are blood cancers?

A

5%

3
Q

How many people are diagnosed with a blood cancer daily in the UK?

A

Approximately 60.

4
Q

What is the most common type of cancer in the age bracket 15-24?

A

Blood cancers (men and women).

5
Q

What is the main cause of cancer death in people aged 1-34 years?

A

Leukaemia/ blood cancers.

6
Q

What proportion of the UK population will die of leukaemia, lymphoma or myeloma?

A

1 in 45 people.

7
Q

What does leukaemia result from?

A

A series of mutations in a single lymphoid or myeloid stem cell.
These mutations lead the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukaemic clone.

8
Q

What is the difference between leukaemia and other cancers?

A

Most cancers exist as a solid tumour.
It is uncommon for patients with leukaemia to have tumours.
Leukaemic cells replace normal bone marrow cells and circulate freely in the bloodstream.
Haemopoietic and lymphoid cells behave differently from other body cells.
Normal haemopoietic stem cells can circulate in the blood- stem cells and cells derived from them can enter tissues.
Normal lymphoid stem cells recirculate between tissues and blood.

9
Q

What is the equivalent of ‘benign’ and ‘malignant’ leukaemia?

A

The concepts of invasion and metastasis cannot be applied to cells that normally travel around the body and enter tissues.
Leukaemias that behave in a relatively ‘benign’ manner are chronic- the disease goes on for a long time.
Leukaemias that behave in a ‘malignant’ manner are acute- if not treated, the disease is very aggressive and the patient dies quite rapidly.

10
Q

How is leukaemia classified?

A

Acute or chronic
Lymphoid or myeloid
Lymphoid can be B or T lineage
Myeloid can be any combination of granulocytic, monocytic, erythroid or megakaryocytic

11
Q

What are the 4 main types of leukaemia?

A

Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)

12
Q

Why do people get leukaemia?

A

Results from a series of mutations in a single stem cell.
Some mutations result from identifiable (or unidentifiable) oncogenic influences.
Others are probably random errors- chance events- that occur throughout life and accumulate in individual cells.

13
Q

What important leukaemogenic mutations have been recognised?

A

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

14
Q

What factors increase the risk of leukaemia developing or contribute to leukaemogenesis?

A

Loss of function of a tumour suppressor gene can contribute to leukaemogenesis- this can result from deletion or mutation of the gene.
If there is a tendency to increased chromosomal breaks, the likelihood of leukaemia is increased.
If the cell cannot repair DNA normally, an error may persist whereas in a normal person the defect would be repaired.

15
Q

Give examples of inherited or other constitutional abnormalities that can contribute to leukaemogenesis.

A

Down’s syndrome
Chromosomal fragility syndromes
Defects in DNA repair
Inherited defects of tumour-suppressor genes

16
Q

Give examples of identifiable causes of leukaemogenic mutations.

A

Irradiation
Anti-cancer drugs
Cigarette smoking
Chemicals- benzene

17
Q

What are the differences between acute and chronic myeloid leukaemia?

A

In AML, cells continue to proliferate but they no longer mature so there is: a build-up of the most immature cells- myeloblasts or ’blast cells’- in the bone marrow with spread into the blood; failure of production of normal functioning end cells such as neutrophils, monocytes, erythrocytes, platelets (for 2 reasons).
In AML, the responsible mutations usually affect transcription factors so that 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.
Cell behaviour is profoundly disturbed.
In CML, the responsible mutations usually affect a gene encoding a protein in the signalling pathway between a cell surface receptor and the nucleus.
The protein encoded may be either a membrane receptor or a cytoplasmic protein.
In CML, cell kinetics and function are not as seriously affected as in AML.
However, the cell becomes 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.
Whereas in AML there is a failure of production of end cells, in CML there is increased production of end cells.

18
Q

What are the differences between acute and chronic lymphoid leukaemia?

A

Acute lymphoblastic leukaemia has an increase in very immature cells- lymphoblasts- with a failure of these to develop into mature T and B cells.
In chronic lymphoid leukaemia, the leukaemic cells are mature, although abnormal, T cells or B cells.

19
Q

How does leukaemia cause the disease characteristics?

A
Accumulation of abnormal cells leading to:
-leukocytosis
-bone pain (if acute)
-hepatomegaly
-splenomegaly
-lymphadenopathy (if lymphoid)
-thymic enlargement (if T lymphoid)
-skin infiltration
Metabolic effects of leukaemic cell proliferation:
-hyperuricaemia and renal failure
-weight loss
-low grade fever
-sweating
Crowding out of normal cells leading to:
-anaemia
-neutropaenia
-thrombocytopaenia
Loss of normal immune function as a result of loss of normal T cell and B cell function- a feature of chronic lymphoid leukaemia.
20
Q

What is the epidemiology of acute lymphoblastic leukaemia?

A

Peak incidence is between 2-8 year olds. Largely a disease of children.
B-lineage ALL may result from delayed exposure to a common pathogen, or early exposure to pathogens protects.
Evidence relates to family size (bigger is better), new towns (mixing populations is bad), socioeconomic class (higher is worse), early social interactions, variations between countries.
In infants and young children, may result from:
-irradiation in utero
-in utero exposure to certain chemicals ? Baygon, ? Dipyrone
-? Epstein-Barr virus infection
Rarely ALL results from exposure to a mutagenic drug.

21
Q

What are the clinical features of acute lymphoblastic leukaemia?

A

Resulting from accumulation of abnormal cells:
-bone pain
-hepatomegaly
-splenomegaly
-lymphadenopathy
-thymic enlargement
-testicular enlargement
Resulting from crowding out of normal cells:
-fatigue, lethargy, pallor, breathlessness (caused by anaemia)
-fever and other features of infection (caused by neutropaenia)
-bruising, petechiae, bleeding (caused by thrombocytopaenia)

22
Q

What are the haematological features of acute lymphoblastic leukaemia?

A

Leukocytosis with lymphoblasts in the blood
Anaemia (normocytic, normochromic)
Neutropaenia
Thrombocytopaenia
Replacement of normal bone marrow cells by lymphoblasts

23
Q

What investigations are performed if acute lymphoblastic leukaemia is suspected?

A

Clinical history and physical examination
Blood count and film
Check of liver and renal function and uric acid
Bone marrow aspirate
Cytogenetic/molecular analysis
Chest x-ray
Immunophenotyping

24
Q

Why is cytogenetic/molecular genetic analysis important in acute lymphoblastic leukaemia?

A

Useful for managing the individual patient because it gives information about prognosis.
Advances knowledge of leukaemia because it has permitted the discovery of leukaemogenic mechanisms.

25
Q

What are the leukaemogenic mechanisms in acute lymphoblastic leukaemia?

A

Translocation leading to formation of a fusion gene.
Dysregulation of a proto-oncogene by juxtaposition of it to the promoter of another gene, e.g. a T cell receptor gene.
Point mutation in a proto-oncogene.

26
Q

How is acute lymphoblastic leukaemia treated?

A
Supportive:
-red cells
-platelets
-antibiotics
Systemic chemotherapy
Intrathecal chemotherapy