Haematology 13 - Acute leukaemia Flashcards
Bone marrow failure
Anaemia
Neutropenia
Thrombocytopenia
Where does the mutation occur in CML?
At the pluripotent haematopoietic stem cell stage therefore during the chronic phase it is characterised by overproduction of myelocytes however when it turns acute it can have a lymphoblastic crisis i.e. CML –> ALL
Which other leukaemia can have a later lymphoblastic crisis?
AML, can sometimes mutate at pluripotent haematopoietic stemm cell point
Types of chromosomal abnormalities in AML
Duplication, chromosomal loss, inversion or translocaitons
Most common chromosomal duplication (trisomy)
Trisomy 8 and trisomy 21, hence increased AML in down’s syndrome
Translocation/inversion in APML
t(15;17), PML-RARA
AML most common inversion/translocation – new fusion genes
t(8;21) –> RUNX1 + RUNX1T1 (AML + ALL)
Most common chromosomal loss/part-deletion in AML
del 5q or del 7q
Leukaemogenesis of chromosomal deletions and AML
Deletion of TSG
Core binding factor AML/ CBF:AML
Inversion 16 (t16;16) –> fusion gene
Many AMLs have aberrations in chromosome structure or count or…
Molecular changes (chromosomes appear normal) (point mutations associated with AML)
Leukaemogenesis in AML, what is needed?
Requires multiple genetics hits - 2 or more molecular changes
Type 1 abnormalities in the leukaemogenesis of AML
Anti-apoptosis as promote proliferation and survival
Type 2 abnormalities in AML
Block differentiation –> survival and proliferation of blast cells
What can result in the failure of differentiation?
Disruption of transcription factor function
2 example of disruption of transcription factor function
t(8;21) (RUNX1), inv(16) (CBF-AML)
What clinical feature could indicate APML in a patient with AML?
Sudden DIC
What is APML classified by?
Excess of abnormal promyelocytes (Auer rods)
What is the variant form of APML characterised by?
Bilobed nuclei
What feature is pathognomic of myeloid neoplasms?
Auer rods
Cytochemistry stains in AML
Myeloperoxidase +
Sudan black
Investigations used to differentiate lymphoid from myeloid
Immunophenotyping
Immunophenotyping markers in AML
MPO, CD13, CD33 (MYELOID MARKERS)
B cell markers
CD19,CD20
