Haem: Acute Leukaemia Flashcards
Which cell level does CML tend to occur in?
Pluripotent haematopoietic stem cell
So affects all myeloid cells and can get lymphoid cells in blast crisis
Which cell level does AML tend to occur in?
Pluripotent haematopoietic stem cell or multipotent myeloid stem cell
List some types of chromosomal abnormalities that are associated with AML.
- Duplications
- Loss
- Translocation
- Inversion
- Deletion
How can altered DNA sequence lead to leukaemia?
- By the creation of a fusion gene - AML and ALL
- By abnormal regulation of genes - ALL
Which chromosomal duplications are most commonly associated with AML?
8 and 21 (there is a predisposition seen in Down syndrome)
Which chromosomal deletions are most commonly associated with AML?
5/5q and 7/7q
q means long arm, number means whole chromosome
List some molecular abnormalities that an occur in apparently normal chromosomes.
- Point mutations
- Loss of function of tumour suppressor genes
- Partial duplication
- Cryptic deletion (formation of a fusion gene by deletion of a small section of DNA)
i.e. not obvious duplication/deletion –> trisomy/monosomy
List some risk factors for AML.
- Familial
- Constitutional (e.g. Down syndrome)
- Anti-cancer drugs –> solid tumour patients can then get AML
- Irradiation
- Smoking
What are type 1 and type 2 abnormalities with regards to leukaemogenesis?
- Type 1: promote proliferation and survival (anti-apoptosis)
- Type 2: block differentation - via disrupting transcription factors
NOTE: leukaemogenesis in AML requires both
What is the main role of transcription factors?
- They bind to DNA, alter the structure to favour transcription and, ultimately, regulate gene expression
- Disruption of transcription factors can result in failure of differentiation
Which chromosomal aberration causes APML?
Translocation 15;17
block in differentiaion a bit late than AML, so excess promyelocytes
What is a characteristic feature of APML? Why does this occur?
- Haemorrhage - this is because APML is associated with DIC and hyperactive fibrinolysis
Name the fusion gene that is responsible for APML.
PML-RARA
In what way are the promyelocytes in APML considered ‘abnormal’?
They contain multiple Auer rods
Describe how the variant version of APML is different from the classical type
- The variant form has granules that are below the resolution of a light microscope
- They also tend to have bilobed nuclei
Which microscopic feature is pathognomonic of myeloid leukemias?
Auer rods
Which stain can be used to distinguish myeloid leukaemias from other leukaemias?
Myeloperoxidase
Name other similar stains that are not used as frequently for myeloid leukaemias (other than myeloperoxidase).
- Sudan black
- Non-specific esterase
No stains for ALL so immunophenotyping done for all now
List the clinical features of AML.
- Bone marrow failure (anaemia, neutropaenia, thrombocytopaenia)
- Local infiltration of leukaemic cells into tissues (splenomegaly, hepatomegaly, gum infiltration, CNS, skin)
- Hyperviscosity if WBC is very high (can cause retinal haemorrhages and exudates)
lymphadenopathy more rare in AML
How does DIC in APML differ from “typical” DIC
less thrombotic features in APML DIC because of the very active fibrinolysis
therefore don’t get things like organ ischaemia or tissue necrosis
Outline the tests that may be used to diagnose AML.
- Blood film - blasts, Auer rods, granules
- Bone marrow aspirate
- Cytogenetic studies (done in EVERY patient) - looking at chromosomes
- Immunophenotyping - look at cell surface markers
- Molecular studies and FISH
What is aleukaemia leukaemia?
When there are no leukaemic cells in the peripheral blood - need bone marrow aspirate to show blasts
Outline the supportive care given for AML.
- Red cells
- Platelets
- FFC/cryoprecipitate in DIC
- Antibiotics - if septic
- Allopurinol (prevent gout when leukaemic cells die following chemotherapy)
- Fluid and electrolyte balance
- Chemotherapy
What are the principles of treatment of AML?
- Damage the DNA of leukaemic cells
- Leave the normal cells unaffected
- Combination chemotherapy is ALWAYS used
- Usually given as 4-5 courses (2x remission induction + 2/3x consolidation)
- Treatment usually lasts around 6 months
