Symposium 2 - Leukaemia Flashcards
Complete the diagram on haematopoiesis
What is G-CSF?
G-CSF promotes neutrophil proliferation
G-CSF = granulocyte colony stimulating factor
What is cancer?
Transformed cell phenotype?
Genetic?
Epigenetic?
Transformed cell phenotype
–Uncontrolled proliferation
–Failure to undergo apoptosis
Genetic
–Oncogenes
–Tumour suppressor genes
Epigenetic
–Dysregulated gene expression
–Aberrant DNA methylation
Complete the diagram on types of DNA mutation
What are the clinical features of leukaemia?
Myelofibrosis (causes massive splenomegaly)
Polycythemia rubra vera (too many red cells)
Essential thrombocythemia (too many platelets)
What does this blood smear show?
- Polycythemia rubra vera
- Myelofibrosis
What does this blood smear show?
Leucoerthyroblastic blood picture
Nucleated RBC and immature leucocytes
What is JAK-STAT signalling?
Signal transduction pathway for EPO and G-CSF
What signalling pathway is mutated in the majority of acute myeloid leukaemia cases?
JAK-STAT signalling
Signal transduction pathway for EPO and G-CSF
Complete the diagram
Why does myelofibrosis cause splenomegaly?
When bone marrow becomes fibrotic, spleen takes over
What is myelofibrosis?
Fibrotic bone marrow
What is a myeloproliferative state?
Overproduction of a type of blood cell
Whats the diagnosis?
Too many white cells - chronic myeloid leukaemia
What chromosome is associated with chronic myeloid leukaemia?
“Philadelphia chromosome”
Chromosome 22->9
t(9;22) translocation
BCR gene from chromosome 22 and ABL gene from chromosome 9 come together.
What test is this?
“FISHing” for CML
FISH = fluorescent in situ hybridisation
What does imatanib target?
The BCR-ABL oncogene
What effect does imatinib have on chronic myeloid leukaemia patients?
Normalises blood counts
Improves survival in CML
Which leukaemia can occasionally turn into AML?
CML
What is acute myeloid leukaemia?
Uncontrolled proliferation of primitive cells in the bone marrow
Name 3 causes of bone marrow failure in acute myeloid leukaemia
–Anaemia
–Infections
–Bleeding
What does this show?
AML
Leukaemic blasts - very high nucleus:cytoplasm ratio
What are the clinical features of AML?
- Anaemia
- Infections
- DIC
- Ulcers
- Infiltration
- Bruising
What are the 5 ways of diagnosing AML?
- Morphology - blood film
- Immunophenotyping
- Genetic
- Cytogenetic
- Molecular
What are the 3 treatments for AML?
Chemotherapy – kills rapidly dividing cells:
Supportive therapy:
–Antibiotics, antifungals
–Transfusions of blood and platelets
Allogeneic stem cell transplantation:
What are the steps for the donor and recipient in a allogeneic stem cell transplant?
What are the 2 options for an allogenic stem cell transplant donor?
Sibling (1-in-4 chance of being a match)
Matched unrelated donor (Anthony Nolan
What chemotherpy is used for AML?
–Combination regimes
–Myelo-ablative cycles of treatment
What 3 supporting measures are needed for AML patients?
How would you manage a patient with neutropenic sepsis?
MEDICAL EMERGENCY – High risk of death
- Blood cultures and blind antibiotic therapy if fever > 38°C
1st line – Tazocin (Piperacillin/Tazobactam) +/- Gentamicin
2nd line – Switch to Meropenem +/- Teicoplanin (for Gram +ve)
3rd line – Add anti-fungal e.g. Ambisome (Amphotericin)
Resuscitate patient with i.v. fluids if hypotensive
May require inotropic support on ITU
In neutropenic sepsis are gram positive or gram negative bacteria more dangerous?
Gram negative
What type of pneumonia can AML patients develop?
Pneumocystis pneumonia
What is graft vs host disease? (acute/chronic)
- Caused by donor/host mismatches in major and minor HLA loci
- Results in acute GVH (<100 days) and chronic GVH (>100 days) post-transplant
How is graft vs host disease prevented?
–T-cell depletion of infused donor cells (graft)
–Immunosuppression of recipient (ciclosporin)
What are the clinical manifestations of graft vs host disease?
–Skin rash, sometimes severe
–Diarrhoea, can be bloody
–Deranged liver function, can lead to liver failure
What is graft vs leukaemia?
•Graft-vs-leukaemia effect is how the stem cell transplant cures leukaemia
_____________ post-Tx can treat relapse by augmenting GVL effect
Donor lymphocyte infusions (DLI)
What mutation occurs as a young baby but takes years to cause AML?
DNMT3A methyltransferase
