Acute Leukaemia Flashcards
What are signs and symptoms of acute leukaemia?
Rapid onset
Early death if untreated
Immature cells (blast cells)
Bone marrow failure:
- Anaemia: Fatigue, pallor, breathlessness
- Neutropenia: Infections
- Thrombocytopenia: Bleeding
What are features of acute myeloid leukaemia?
Increases with age
Prognosis worse with increasing age
40% of adults cured
Which chromosomal translocations are associated with acute myeloid leukaemia?
t(15;17)
t(5;8)
Which chromosomal inversion is associated with acute myeloid leukaemia?
A chromosomal inversion, inv(16)
What is the association between chromosomal duplication and AML?
Common in AML
Disease hotspots: +8 and +21 give predisposition
Possible dosage affect – extra copies of proto-oncogenes
What is the association between chromosomal loss or deletion and AML?
Common in AML
Disease hotspots: Deletions and loss of 5/5q & 7/7q
Possible loss of tumour suppressor genes.
Alternative explanation ‒ one copy of an allele may be insufficient for normal haemopoiesis. Possible loss of DNA repair systems.
What are the molecular abnormalities in patients with apparently normal chromosomes which can result in AML?
Point mutation: NPM1, CEBPA
Loss of tumour suppressor genes
Partial duplication: FLT3
Cryptic deletion
What are risk factors for AML?
Familial or constitutional predisposition
Irradiation
Anticancer drugs
Cigarette smoking
Unknown
What is leukaemogenesis in AML?
Multiple genetic hits
At least 2 interacting molecular defects
Synergise to give leukaemic phenotype
What are the two types of abnormalities in leukaemogenesis in AML?
Type 1 abnormalities: Promote proliferation and survival.
Type 2 abnormalities: Block differentiation (which would normally be followed by apoptosis).
How is differentiation affected in AML?
Transcription factors:
- Bind to DNA
- Alter structure to favour transcription
- Regulate gene expression
If transcription factor function is disrupted, cells cannot differentiate.
What can be seen in t(8,21) AML?
With this particular chromosomal abnormality there is some maturation; these are not all blast cells.
What can be see in inv(16), t(16;16) AML?
In this genetic subtype there is some maturation to bizarre eosinophil precursors with giant purple granules.
What can be seen in acute promyelocytic leukaemia with t(15;17)?
A very special type of acute leukaemia.
The molecular mechanism is understood, thus molecular treatment can be applied. The great majority of patients can now be cured.
An excess of abnormal promyelocytes.
Disseminated intravascular coagulation (DIC).
Two morphological variants but the same disease.
What are the two types of abnormalities in acute promyelocytic leukaemia?
Type 1 abnormalities: FLT3 -ITD
Type 2 abnormalities: t(15;17) PML-RARA
