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Biology Of Cancer > Leukaemia And Lymphoma > Flashcards

Leukaemia And Lymphoma Flashcards

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1
Q

Where are B cells produced?

A

In the bone marrow

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2
Q

What happens once B cells have been produced?

A

Selected into the peripheral blood
Travel to secondary lymphoid organs eg lymph nodes and spleen
Recruited into germinal centres if there is an antigen present

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3
Q

What is in the cortex of lymph nodes?

A

B and T cells

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4
Q

What is in the medulla of lymph nodes?

A

Plasma cells
Macrophages
B cells
Sinuses which lymph can flow into

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5
Q

What are the different types of lymphocytes?

A

B and T cells

Natural killer cells

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6
Q

What happens if there is an antigen in a lymph node?

A

B cells are recruited to the germinal centre (follicles found in the cortex)
B cells evolve and produce high affinity antibodies to resist infections

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7
Q

What happens in somatic hypermutation?

A

When deaminase enzymes introduce point mutations onto the variable region of DNA that codes for the antibody
Introduces uracil to the DNA
Uracil then excised and swapped for a different base

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8
Q

How do mutations accumulate in somatic hypermutation?

A

Uracil base swapped in then replaced
B cells proliferate and mutations accumulate so that there are many different receptors with different affinities for the antigen

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9
Q

After proliferation of B cells, how are they selected and what happens to them?

A

The B cell with the highest affinity is selected and differentiates into plasma cells to produce antibodies

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10
Q

What is class switching antibodies and why does it happen on B cells?

A

IgM switches to IgG
The on is changes, variable region stays the same so affinity stays the same
Allows the antibody to interact with different effector molecules
Requires deaminase again

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11
Q

Why are lymph nodes a ‘perfect storm’ for cancer?

A

Have intense proliferation of B cells with many mutations being produced

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12
Q

What type of lymphoma is Burkitt’s?

A

A non-Hodgkin’s lymphoma

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13
Q

What forms of burkitt’s can you get and what is the geographical distribution?

A

Sporadic happen in the west

Epidemic more common in Africa

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14
Q

What is Burkitt’s lymphoma associated with?

A

EBV

Malaria

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15
Q

What is the mutation in Burkitt’s lymphoma?

A

The translocation of the MYC gene from chromosome 8 to 14, causing it to be expressed

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16
Q

Why can the MYC gene easily by translocated in Burkitt’s lymphoma?

A

Found close to constant regions
Enhancer elements normally drive transcription of these genes (antibody genes), can also drive MYC genes, causing it to be expressed

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17
Q

What does the MYC gene code for?

A

A transcription factor which causes proliferation of the cell

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18
Q

How can the translocation in Burkitt’s lymphoma be detected?

A

Fluorescence in situ hybridisation

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19
Q

What is FISH?

A

Labelled single-stranded DNA can interact with sufficiently similar complementary sequences to form complexes/hybrids
This allows specific sequences/genes to be detected

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20
Q

Who is follicular lymphoma typically seen in?

A

Older people

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21
Q

How do people with follicular lymphoma typically present?

A

Lymphadenopathy
Weight loss
Night sweats

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22
Q

How is follicular lymphoma treated?

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A

Observation as it is very slow growing

23
Q

What is seen histologically in follicular lymphoma?

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A

Atypical neoplasticism follicles

Different sizes

24
Q

What is the mutation in follicular lymphoma?

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A

Translocation of the BCL-2 gene from 14 to 18

25
What is the result of the mutation in follicular lymphoma?
The BCL-2 gene comes under the influence of the enhancer, so is permanently switched on and over expressed.
26
What does the BCL-2 gene do?
Important in the intrinsic pathway of apoptosis | Prevents the association of BAC and BAX at high levels, stopping apoptosis
27
What does the mutation to BCL-2 in follicular lymphoma cause?
An expanded pool of cells in the germinal centre, within which further mutations leading to cancer can occur Neoplastic infiltrate grows in atypical follicles and is composed of centrocytes and centroblasts
28
How is the pool of cells expanded in Burkitt's lymphoma and follicular lymphoma in general?
Burkitt's - have more cells going in than are dying Follicular - normal amount going in but cells are resistant apoptosis
29
When does diffuse large B cell lymphoma normally occur?
Middle-age onwards
30
How is diffuse large B cell lymphoma treated?
Chemotherapy | It is high grade and aggressive
31
What is the mutation in diffuse large B cell lymphoma?
A translocation between 3 and 14 | Causes the antibody heavy chain enhancer to drive expression of BCL-6 which prevents apoptosis of B cells
32
Why is diffuse large B cell lymphoma without a translocation given a worse prognosis?
Because the translocation is a target area of treatment
33
Characteristics of mantle cell lymphoma?
Aggressive but low grade
34
Mutation in mantle cell lymphoma?
Translocation between 11 and 14 Get over expression of cyclin D1 Allows progression their the cell cycle, past the first G1 checkpoint
35
Which lymphoma is only seen in immunosuppressed patients?
Primary effusion lymphoma - transplant patients - AIDS patients
36
Which virus causes primary effusion lymphoma?
KSHV
37
How does the KSHV virus lead to primary effusion lymphoma?
A combination of the virus and poorly characterises cellular genetic changes KSHV can produce GPCRs which lead to proliferation and cancer
38
Which virus can cause adult T-cell leukaemia lymphoma?
HLTV-1
39
Where is adult T cell leukaemia lymphoma seen?
In the distribution of the HLTV-1 virus - southern Japan - equatorial Africa - Malaysia - Caribbean - South America - southern US
40
What are the different clinical forms of adult T cell leukaemia lymphoma?
Acute Chronic Smouldering Lymphoma
41
How does HLTV-1 cause adult T cell leukaemia lymphoma?
Loss of Tax expression | Continuous expression of HBZ gene
42
What do myeloid cells give rise to?
``` Red blood cells Platelets Granulocytes which differentiate into -basophils -eosinophils -neutrophils ```
43
What is leukaemia?
Malignancy of leukocytes (not lymphocytes!)
44
What is the mutation in chronic myeloid leukaemia?
Translocation from chromosome 9 to 22 - Philadelphia chromosome Moves the ABL gene next to the BCR gene BCR-ABL fusion protein formed Causes proliferation
45
What happens in chronic myeloid leukaemia?
Proliferation of pluripotent haemopoietic stem cells | Get proliferation and failed apoptosis
46
What is the most common haematological malignancy?
Diffuse large B cell lymphoma
47
How is gene expression profiling done?
RNA is extracted and complementary DNA is labelled and hybridised to a chip The chip is scanned and different colours are quantified to produce heat maps Different colours can show high and low expression due to varying levels of mRNA present
48
How is comparative genome hybridisation done?
Patient DNA is hybridised to reference DNA | If there is a change or deletion, it is harder to hybridise
49
What is looked at in array comparative genomic hybridisation? (Array CGH)
Screen for sub-microscopic chromosomal deletions for which the locus cannot be deduced from the patient's phenotype
50
How is array CGH done?
An array of DNA probes covering the entire genome are applied to a solid matrix Patient DNA and control DNA are labelled with different coloured fluorescent tags The control and patient DNA are hybridised to the probe array Where normal DNA exceeds that of the patient's DNA, the patient has a deletion of that chromosomal region
51
What does array CGH show in DLBCL and why?
Loss of the long arm on chromosome 6 This is where BLIMP-1 is which is involved in B cell differentiation Without BLIMP, the B cell stays germinal centre This and high BCL-6 levels which is required to keep cells in the GC leads to lots of cells
52
What can flow cytometry be used for?
Diagnosis of B cell lymphoma Gives information about how many cells of a particular type are present Can see different levels of expression of different CD genes by different types of B cell lymphomas and can be used for diagnosis
53
How is flow cytometry done?
Cells stained with a monoclonal antibody which emits light | Cells sent in single file throng a chamber and hit with a laser

Biology Of Cancer (13 decks)

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