Genetics In Diagnosis Of Haematological Malignancies

Question 1

What defines a clonal disease?

Answer 1

When changes occur in a cell that confer a selective advantage - the cell divides and becomes a clone

Question 2

What are some common symptoms observed in haematological malignancies?

Answer 2

• Lumps (typical of lymphoma)
• Bone fractures and kidney problems (typical of myeloma)
• Fatigue, vulnerability to infection (common in all but more severe in leukaemia)

Question 3

What is the difference in where the changes to the cell occur in:

1. Leukaemia
2. Lymphoma
3. Myeloma

Answer 3

1. Cells in the bone marrow
2. Cells in the lymph nodes or other parts of immune system
3. Plasma cells which have returned to BM following antigen activation in lymph nodes/spleen

Question 4

What are the genetic risk factors associated with haematological malignancies?

Answer 4

• Down’s syndrome
• Blooms
• Fanconi anaemia
• Ataxia telangiectasia
• Neurofibromatosis
• Klinefelters
• Familial tendency for AML, CLL, HL and non-HL

Question 5

What are some of the environmental risk factors associated with haematological malignancies?

Answer 5

• Lymphomas = radiation exposure
• AML/MDS = benzene use
• Secondary leukaemia = therapy related (chemo/radiotherapy used to treat primary cancer)

Question 6

What is cell phenotyping in the context of haematological malignancies?

Answer 6

• Assessment of cell surface expression of CD (cluster of differentiation)
• Very important in determining type of disease (myeloid/lymphoid) and the stage of cell development that is blocked

Question 7

Describe the use of quantitative (real time) PCR for diagnosis of haematological malignancies

Answer 7

• By following progression of a PCR we can look at when a product is first detected and calculate how much template was there initially
• For example, a product detected at an earlier cycle indicates more starting material was present
• used for minimal residual disease monitoring