Physiology: cancer

Question 1

C myc oncogene and Burkitt’s lymphoma
- Normal function of the C-myc gene?

• What somatic recombination event occurs for Burkitt’s lymphoma?
• How does this lead to Burkitt’s lymphoma?

Answer 1

• Turning on genes associated with cell division
• The B cell receptor gene (on chromosome 14) undergoes somatic recombination (VDJ recombination) with the c-myc gene on chromosome 8.
• Leads to overexpression of c-myc protein –> hyperproliferation of B cells –> Burkitt’s lymphoma

Question 2

Follicular lymphoma
- What somatic recombination event occurs for Bcl-2?

Answer 2

In follicular lymphoma, there is a mistake in VDJ/somatic recombination

Bcl-2 is translocated from chromosome 18 into the heavy chain locus of chromosome 14 –> overexpression of Bcl-2

Question 3

Chronic lymphocytic leukemia
- Impact on venetoclax on Bcl-2?

Answer 3

Inhibits –> apoptosis of cancer cell

Question 4

Role of telomeres and telomerase - in cell age and cancer?

Answer 4

Erosion of telomeres leads to cell ageing.
Telomerase restores –> promotes cancer.

Question 5

Leukemia
- Cell type? Location?
- Symptoms?
- Complications?

Answer 5

Leukocytes - any WBC; usually in the bone marrow and blood
Lymphadenopathy, bone marrow infiltrates, meningeal lesions
Bone marrow failure, anemia, bleeding, infection

Question 6

Lymphoma
- Cell type?
- Location?

Answer 6

Cancers of lymphocytes (B, T, NK cells) within the lymphatic system (usually lymph nodes)

Note that malignant lymphocytes can overspill from the lymphoma and enter the circulation

Question 7

Myeloma
- Cell type?
- What protein do they secrete?
- Effects?

Answer 7

Plasma cells (not myeloid cells)
Paraproteins (basically monoclonal antibodies)
Bone destruction/bone marrow lesions, kidney damage

Question 8

Are malignancies more common in B or T cells? Why?

Answer 8

B cells
There are increased chances of mutations - due to affinity maturation and isotype switching

Question 9

Acute lymphoblastic leukemia
- What cells?
- Early or late onset?
- Mild or aggressive?
- Symptoms?
- Is it curable?

Answer 9

Circulating balst cells in the blood (usually from precursor B cells)
Early onset (most frequent childhood leukemia)
Aggressive

Low RBC - lethargy, anorexia
Low platelets - bleeding (nose and gums)
Lymphocyte buildup - hepatosplenomegaly, lymphadenopathy
Fever (infection)

Yes, it is curable

Question 10

Chronic lymphocytic leukemia
- What cells?
- Early or late onset?
- Mild or aggressive?
- Symptoms?
- Is it curable?

Answer 10

High levels of partially mature B cells
Later onset (the most frequent form of adult leukemia)
Less aggressive
Similar to acute lymphoblastic leukemia
- No (treatable but incurable)

Question 11

Chronic lymphocytic leukemia
- Treatments

Answer 11

Fludarabine (FCR): a purine analogue that interferes with DNA replication

Cyclophosphamide: an alkylating agent that crosslinks DNA, preventing replication leading to apoptosis

Rituximab - a mAb specific to B cells

Question 12

Leukemia - general treatments?

Answer 12

Surgery
Chemotherapy
Prophylactic antibiotics, anti virals, anti fungals
Bone marrow transplants
GM-CSF
Immunotherapies eg. rituximab