Cancer Case Studies Flashcards
How may a patient with chronic myeloid leukaemia present?
There may be palpable splenomegaly on inspection but the patient may be asymptomatic on presentation for a check-up
How may chronic myeloid leukaemia present in a blood test?
There may be elevated WBC (leukocytes), low haemoglobin, elevated platelets
Describe the pathogenesis of chronic myeloid leukaemia
This is a disease of haematopoietic stem cells which leads to increased production of neutrophils, eosinophils, basophils and platelets (from megakaryocytes)
What cells may be more present on histology specimen in chronic myeloid leukaemia?
More neutrophils, eosinophils, basophils (mast cells) and platelets (so more megakaryocytes) as these are derived from the myeloid stem cells
What genetic criterion is necessary to give a diagnosis of chronic myeloid leukaemia?
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
How is abelson tyrosine kinase implicated in chronic myeloid leukaemia?
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
Describe the clinical phases of chronic myeloid leukaemia
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
Name the three clinical phases of chronic myeloid leukaemia
Chronic phase, accelerated phase and blast crisis
Name three treatments which may be used in the treatment of chronic myeloid leukaemia
Chemotherapy, allogeneic stem cell transplantation and signal transduction inhibitors such as tyrosine kinase inhibitors (TKIs)
Name one first generation TKI that may be used in the treatment of chronic myeloid leukaemia
Imatinib
What is imatinib?
It’s a first generation TKI that may be used in the treatment of CML
Describe the mechanism of action of imatinib in the treatment of CML
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
Name two second generation TKIs that may be used in the treatment of CML
Nilotinib and dasatinib
Name two third generation TKIs that may be used in the treatment of CML
Ponatinib and bosutinib
What is one potential clinically important use of the third generation TKI ponatinib in the treatment of CML?
May be used in CML types that have become resistant to treatment due to the T315I mutation
How may CML patients become resistant to TKI treatment?
If the patient develops the T315I mutation in the Bcr-Abl gene (abelson tyrosine kinase) then they will be resistant to (almost) all TKIs
How may a patient with lymphoma present?
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.
How may the bloods appear with someone with lymphoma?
These may vary depending on the severity of the condition, but they will have elevated LDH and CRP levels most likely
Describe the pathogenesis of lymphoma
Increased proliferation of lymphocytes
Name the four main classes of lymphoma
Hodgkin lymphoma, aggressive B-cell non-hodgkin lymphoma, indolent B-cell non-hodgkin lymphoma and T-cell non-hodgkin lymphoma
Describe aggressive B-cell non-hodgkin lymphoma
There is rapid proliferation of the cells and requires immediate chemotherapy which may lead to cure of the disease
Describe indolent B-cell non-hodgkin lymphoma
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
What is blinatumomab and how may it be used in the treatment of lymphoma?
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
Name an example of an mTOR inhibitor that may be used to treat lymphoma
Temsirolimus
How may drugs such as thalidomide and lenalidomide be used in the treatment of lymphoma?
These are immunomodulating agents which work to co-stimulate T cells and activate natural killer cells to target the cancer
Name an example of an proteasome inhibitor that may be used to treat lymphoma
Bortezomib
How may rituximab be used in the treatment of lymphoma?
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
What is rituximab?
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
