8. Haematological malignancies

Question 1

What are the two lineages for blood cells?

Answer 1

Myeloid

Lymphoid

Question 2

When does a leukaemia develop?

Answer 2

When the blood cell does not complete differentiation - gets stopped in an earlier stage and starts to proliferate

Question 3

What are the two mutations required for a leukaemia to develop?

Answer 3

Loss of function of transcription factors required for differentiation - differentiation block
Gain of function mutations of tyrosine kinases - enhanced proliferation

Question 4

What are the clinical features of leukaemia?

Answer 4

Anaemia - fatigue and shortness of breath
Low platelets - bleeding
Neutropenia - bacteria and fungal infections
Tissue infiltration - bone pain

Question 5

What is the most common childhood leukaemia?

Answer 5

ALL - acute lymphoblastic leukaemia

Question 6

Define acute leukaemia

Answer 6

Accumulation of precursor cells (blasts) with a high growth rate

Question 7

Define chronic leukaemia

Answer 7

Accumulation of mature cells with a failure of apoptosis

Question 8

At what stage can leukaemia no longer be treated?

Answer 8

Once they cross the BBB and enter the CNS - chemotherapeutic agents cannot cross the BBB

Question 9

What is the mutation associated with chronic myeloid leukaemia (CML)?

Answer 9

Philadelphia chromosome - shortened chromosome 22

Also involves chromosome 9 (9:22 translocation)

Question 10

What is the main pharmacological treatment for cancer?

Answer 10

Imatinib - SMTKI

Question 11

What are the different forms of mAbs used for treatment?

Answer 11

Unconjuctated
Coupled to toxins
Coupled to radioisotopes

Question 12

Why can some mAbs only be used once?

Which mAbs are these?

Answer 12

Patients develop human anti-mouse antibodies (HAMA)

Murine mAbs

Question 13

What are the three ways in which mAbs can destroy cancer cells?

Answer 13

Antibody-dependent cell-mediated cytotoxicity (ADCC)
Complement-dependent cytotoxicity
Apoptosis