Haematology - Genetics and Chemotherapy

Question 1

Chemotherapy: name 3 antimetabolites, give MOA (for 2) and important SEs (for 2)

Answer 1

• Methotrexate: inhibit pyrimidine or purine synthesis or incorporation into DNA
  
  • SE: mouth ulcers, gut toxicity
• 6-Mercaptopurine: purine analogue
  
  • Jaundice, gut toxicity
• Hydrocycarbamide: inhibits ribonucleotide reductase

Question 2

Chemotherapy: Name 5 alkylating agents and their MOAs (2) and important SEs (2)

Answer 2

• Cyclophosphamide: crosslink DNA, impede RNA formation
  
  • SE: haemorrhagic cystitis, cardiomyopthy, marrow aplasia, hepatic toxicity
• Cisplatin: intrastrand DNA linkage
  
  • SE: Renal dysfunction, neurotoxicity and ototoxity
• Others: chlorambucil, busulfan, bendamustine

Question 3

Chemotherapy: plant derivatives - name one important plant derivative drug and SEs

Answer 3

• Vincristine: causes spindle damage
  
  • SE: neuropathy (peripheral, bladder, gut), myelosuppression

Question 4

What are tyrosine kinases? Why are these important?

Answer 4

• Wnzymes, which phosphorylate proteins on tyrosine residues, and are important as cell receptors and intracellular signalling.
• Many underlie large number of haematological malignancies eg JAK2

Question 5

What are oncogenes? How do these arise?

Answer 5

• Arise because of gain-of-function mutations in normal cellular genes called proto-oncogenes.
• Proto-oncogenes are involved in a lot of cellular processes, often in the pathway by which external signals are transduced to the cell nucleus to activate genes.
• Oncogenic versions are generated when activity of proto-oncogenes is increased or acquire new function (mutation, translocation, duplication)

Question 6

Chemotherapy: cytotoxic antibiotics - name 2 important ones, give MOA and important SEs

Answer 6

• Anthracyclines: bind to DNA and interfere with mitosis
  
  • SE: cardiac toxicity and hair loss
• Bleomycin: DNA breaks
  
  • SE: pulmonary fibrosis and skin pigmentation

Question 7

What are tumour suppressor genes? Why are these important for malignancies?

Answer 7

• May acquire loss of function mutations (point mutation or deletion), which lead to malignant transformation.
• Often act as components of mechanism that regular entry of cell from G1 to S phase or passage through S phase to G2 and mitosis

Question 8

What is the MOA of rituximab? Give some SEs

Answer 8

• Anti-CD20 - induces apoptosis of cells
• SEs: infusion reactions, immunosuppression

Question 9

Give some side effects of corticosteroids (6)

Answer 9

• PUD
• Obesity
• DM
• Osteoporosis
• Psychosis
• HTN