L11: Chronic Myeloid Leuaemia From Chromosome To Targeted Therapy Flashcards
What is chronic myeloid leukaemia
Excess myeloid cells
What is a philadelphia
A reciprocal chromosome
What is the Philadelphia of CML
Chromosome 22 and 9
In a blood film with someone with CML what would it show
Normal neutrophils Precursors of: Metameylocytes Myelocytes Premyelocytes Blasts
What would a cml bone marrow aspirate show
Lots of cells together
Would would a cml bone marrow trophine show
Packed marrow with less fat (should have more fat)
Which chromosome does BCR gene lie on
Chromosome 22
What chromosome does ABL gene lie on
Chromosome 9
What happens to BCR and ABL
Fuse together to from a new gene called BCR-ABL on chromosome 22
How does BCR and ABL fuse
Via translocation
What does the expression of BCR-ABL lead to
Increased proliferation
Decreased apoptosis
What is the typical presentation of BCR-ABL
Asymptomatic - can be incidental High viscosity of haematocrit- gives rise to heart failure, bleeding back of eye and renal failure Anaemia- tiredness Infection- WBC do not function properly Bleeding- due to decreased platelets Weight loss Splenomegaly
What are the 3 basic diagnosis technique we can use to diagnose CML
- blood count and film
- biochemistry
- bone marrow diagnosis
What would a blood count and film show for the levels of haemotcrit
High levels of WBC
Low/high platelet
Low haemoglobin
What would the biochemistry test show
Abnormal liver
Impaired renal function
Raised lactate dehydrogenase
What other disease do we need to exclude
Bacterial infection
Other malignancy
How can we look for BCR-ABL gene
By FISH (fluorescence in situ hybridisation)
Describe what occurs in FISH
1) place a piece of dna
2) put primers of BCR and ABL
3) heat dna
4) primers will join to BCR and ABL and light up with fluorescence
To find out how much BCR-ABL gene there is what test can be carried out
Real time quantitative PCR
What is the acute treatment of CML
Hydoxylurea Leukapheresis (taking WBC out to bring levels down) Allopurinol (to treat gout) Iv fluid (renal failure) Analgesia
What are the long term treatment of cml
Tyrosine kinase inhibitors
Name a common example of tyrosine kinase inhibitor used in CML
Imatinib
Where does imatinib bind to
ABL kinase pocket
What does imatinib prevent
ATP from binding to the ABL tyrosine kinase so ABL cannot be phosphorylated and is inactive
