Leukaemia Symposium

Question 1

What are the clinical features of Acute Myeloid Leukemia?

Answer 1

• Polycythemia: too many red cells, get a flushed face in patients with a lighter complexion
• Myelofibrosis: massive spleen
• Thrombocythemia: too many platelets

Question 2

What is JAK-STAT signalling

Answer 2

Janus kinase/signal transducers and activators of transcription

• mediates cellular responses to cytokines i.e IL-6 and growth factors EGF
• mutations in JAK2 in various cells can cause various presentations of AML

Question 3

What does the JAK2 mutation lead to in Red cell precursors?

Answer 3

• Polycythaemia Rubra vera,
• in 30% of cases, this leads to Primary myelofibrosis
• 5% of cases this s indicative of AML

Question 4

What does the JAK2 mutation lead to Megakarycocytes?

Answer 4

• Essential thrombocythaemia
• in 10-20% of cases associated with Primary myelofibrosis
• also a mutation in reactive fibrosis
• in 10% of primary myelofibrosis indicative of AML

Question 5

What is chronic myeloid leukaemia and what is its genetic origin?

Answer 5

• when there are too many white cells
• mutation in chromosome 22 - Philadelphia chromosome
• translocation between chromosome 9 and 22 t(9;22)

Question 6

How does the genetic mutation for CML work?

Answer 6

• mutation in Chromosome 22 generates a chimeric oncogene in which BCR and c-ABL genes are fused
• BCR/ABL has elevated tyrosine kinase activity
• Tyrosine kinase is responsible for maintaining proliferation, inhibiting differentiation and conferring resistance to cell death

Question 7

What treatment can best be used against CML and what is its action?

Answer 7

• Imatinib (Gleevec)
• a tyrosine kinase inhibitor
• a kinase is an enzyme that promotes cell growth,
• imatinib binds to its active site, antagonist to GRB-2, SHC etc.

Question 8

What is leukaemia?

Answer 8

• it is an uncontrolled proliferation of primitive cells in the bone marrow
• it can cause, bleeding, anaemia and infections

Question 9

What are the clinical features of leukaemia

Answer 9

• Anaemia
• Infections
• DIC
• Ulcers
• Infiltration
• Bruising

Question 10

How is leukaemia diagnosed?

Answer 10

• Bone marrow biopsy
• cytogenetics
• morphology of blood samples
• Immunophenotyping

Question 11

How is AML treated?

Answer 11

• Chemotherapy
• Supportive therapy: antibiotics, antifungals, transfusions of blood and platelets. Indwelling Hickman line
• Stem cell transplantation: autograft, Allograft, sibling or matched donor

Question 12

What is Neutropenic Sepsis?

Answer 12

• a complication of neutropenia (low neutrophil counts
• temp. > 38 degrees
• symptoms and signs of sepsis
• absolute neutrophil count of 0.5x 10⁹
• gram -ve bacteria are most dangerous e.g Pseudomonas

Question 13

Go through the 1st 2nd and 3rd line treatment for neutropenic sepsis.

Answer 13

1. Tazocin (Piperacillin/Tazobactam) +/- Gentamicin
2. Switch to Meropenem +/- Teicoplanin (for Gram +ve)
3. add anti-fungal e.g Ambisome (amphotericin)

Question 14

What is Pneumocystis pneumonia?

Answer 14

• lung infection, acquired by those who are immunosuppressed
• caused by yeast-like fungus Pneumocystis jirovecii

Question 15

What is graft-vs-host disease?

Answer 15

• an immune condition that occurs after transplant procedures, immune cells of donor attacks host’s recipient cells