Cancer Case Studies

Question 1

How may a patient with chronic myeloid leukaemia present?

Answer 1

There may be palpable splenomegaly on inspection but the patient may be asymptomatic on presentation for a check-up

Question 2

How may chronic myeloid leukaemia present in a blood test?

Answer 2

There may be elevated WBC (leukocytes), low haemoglobin, elevated platelets

Question 3

Describe the pathogenesis of chronic myeloid leukaemia

Answer 3

This is a disease of haematopoietic stem cells which leads to increased production of neutrophils, eosinophils, basophils and platelets (from megakaryocytes)

Question 4

What cells may be more present on histology specimen in chronic myeloid leukaemia?

Answer 4

More neutrophils, eosinophils, basophils (mast cells) and platelets (so more megakaryocytes) as these are derived from the myeloid stem cells

Question 5

What genetic criterion is necessary to give a diagnosis of chronic myeloid leukaemia?

Answer 5

There is a reciprocal translocation between chromosome 9 and 22 (philadelphia chromosome) which leads to persistently active Abelson tyrosine kinase expression; this means this kinase can continue to activate substrates and drive proliferation

Question 6

How is abelson tyrosine kinase implicated in chronic myeloid leukaemia?

Answer 6

There is a translocation mutation between chromosome 9 and 22 which leads to the persistent activity of abel son tyrosine kinase so it continues to activate substrates via phosphorylation and leads to tumour cell proliferation

Question 7

Describe the clinical phases of chronic myeloid leukaemia

Answer 7

Chronic phase - asymptomatic and lasts for three to five years
Accelerated phase - this is where blast cells begin to accumulate as well as basophils and platelets and lasts for 12 to 18 months
Blast crisis phase - where blasts account for more than 30% of the total cells and this usually lasts 3 to 9 months

Question 8

Name the three clinical phases of chronic myeloid leukaemia

Answer 8

Chronic phase, accelerated phase and blast crisis

Question 9

Name three treatments which may be used in the treatment of chronic myeloid leukaemia

Answer 9

Chemotherapy, allogeneic stem cell transplantation and signal transduction inhibitors such as tyrosine kinase inhibitors (TKIs)

Question 10

Name one first generation TKI that may be used in the treatment of chronic myeloid leukaemia

Answer 10

Imatinib

Question 11

What is imatinib?

Answer 11

It’s a first generation TKI that may be used in the treatment of CML

Question 12

Describe the mechanism of action of imatinib in the treatment of CML

Answer 12

Competitively binds to the active site of the Abelson tyrosine kinase domain to inhibit the protein and stop it from activating substrates and therefore prevents promotion of tumour cell proliferation

Question 13

Name two second generation TKIs that may be used in the treatment of CML

Answer 13

Nilotinib and dasatinib

Question 14

Name two third generation TKIs that may be used in the treatment of CML

Answer 14

Ponatinib and bosutinib

Question 15

What is one potential clinically important use of the third generation TKI ponatinib in the treatment of CML?

Answer 15

May be used in CML types that have become resistant to treatment due to the T315I mutation

Question 16

How may CML patients become resistant to TKI treatment?

Answer 16

If the patient develops the T315I mutation in the Bcr-Abl gene (abelson tyrosine kinase) then they will be resistant to (almost) all TKIs

Question 17

How may a patient with lymphoma present?

Answer 17

May present with a variety of conditions dependent on the location of the lymphoma i.e. if the lymphoma is in the mediastinum it may lead to upper venous congestion etc.

Question 18

How may the bloods appear with someone with lymphoma?

Answer 18

These may vary depending on the severity of the condition, but they will have elevated LDH and CRP levels most likely

Question 19

Describe the pathogenesis of lymphoma

Answer 19

Increased proliferation of lymphocytes

Question 20

Name the four main classes of lymphoma

Answer 20

Hodgkin lymphoma, aggressive B-cell non-hodgkin lymphoma, indolent B-cell non-hodgkin lymphoma and T-cell non-hodgkin lymphoma

Question 21

Describe aggressive B-cell non-hodgkin lymphoma

Answer 21

There is rapid proliferation of the cells and requires immediate chemotherapy which may lead to cure of the disease

Question 22

Describe indolent B-cell non-hodgkin lymphoma

Answer 22

The disease is slowly progressing and requires a watch and wait approach in the asymptomatic patient but chemotherapy can’t be used as a treatment and it’s often difficult to cure

Question 23

What is blinatumomab and how may it be used in the treatment of lymphoma?

Answer 23

It’s a bivalent antibody that will bind to the CD19 receptor on the affected B cells and also to the CD3 receptor on cytotoxic T cells to lead to apoptosis

Question 24

Name an example of an mTOR inhibitor that may be used to treat lymphoma

Answer 24

Temsirolimus

Question 25

How may drugs such as thalidomide and lenalidomide be used in the treatment of lymphoma?

Answer 25

These are immunomodulating agents which work to co-stimulate T cells and activate natural killer cells to target the cancer

Question 26

Name an example of an proteasome inhibitor that may be used to treat lymphoma

Answer 26

Bortezomib

Question 27

How may rituximab be used in the treatment of lymphoma?

Answer 27

It may be used alongside chemotherapy; it will bind to the CD20 receptor on the B cells involved in lymphoma, and then leads to CDC, ADCC and direct cell death

Question 28

What is rituximab?

Answer 28

A form of monoclonal antibody against CD20 which is often present on B cells (involved in lymphoma) and leads to complement dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and direct cellular death