acute leukaemia Flashcards
what is acute leukaemia
A neoplastic condition characterized by
* Rapid onset
* Early death if untreated
* Immature cells (blast cells)
* Bone marrow failure – blast cell replace normal haematopoeitic tissue:
- Anaemia: fatigue, pallor, breathlessness
- Neutropenia: infections
- Thrombocytopenia: bleeding
Summarise haematopoietic stem cell lineage
Highlight the cell that gives rise to the leukaemia clone
AML – occur in pluripotent stem cell, multipotent, of committed to granulocyte-monocyte lineage
B-ALL - cell committed to B lineage
T-ALL - cell committed to T lineage
CLL – later cell in B lineage
leukaemia in pluripotent stem cell means -> lymphoid and myeloid cell as part of leukaemia - mixed phenotype acute leukaemia
CML - philidelphia +ve and BCRable +ve condition - possible for lymphoid differation and lymphoblastic transformation
Describe this picture
Dominant blast cell
Top – delicate granules = myeloid
Bottom – no granules, smaller blast cells, denser - lymphoid
epidemiology of AML
increase with age
Px worse with age - due to type of leukaemia and frailty
40% of adults cured
principles of chr abnormalities in AML
aberration in count or structure
these are recurrent and -> involved in development of leukamia
Molecular change – chr look ok, but when analysed for DNA then the mutation is found
- duplication
- loss
- translocation (Reciprocal translocation – if one moves back in the opposite direction)
- inversion - 2 breaks and it flips over and joins
- deletion of part of a chr
translocation in acute promyelocytic leukaemia
chr 15 and 17
abnormal 15 gets longer - extra band
17 - shorter
Abnormal is called the ‘derivitive’ takes name from centromere
translocation in acute promyelocytic leukaemia
chr 15 and 17
abnormal 15 gets longer - extra band
17 - shorter
Abnormal is called the ‘derivitive’ takes name from centromere
example of chr inversion
Difficult to recognise – confirm with molecular analysis
effect of translocations and inversions in leukaemia
Altered DNA sequence
* creation of new fusion genes (AML and ALL)
* abnormal regulation of genes (mainly ALL) – gene under influence of promotor/enhancer of another gene
chr duplication in leukaemia
Common in AML
Disease hotspots
* +8 is common (trisomy 8)
* +21 gives predisposition - both neonatal and acute megakaryoblastic leukaemia in young children
Possible dosage affect - extra copies of proto-oncogenes
definition of oncogene
gene that contribute tio causing neoblastic condition
definition of proto-oncogene
potential to develop into oncogene
chr loss or deletion in leukaemia
Common in AML
Disease hotspots - deletions and loss of 5/5q & 7/7q (long arms)
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
![!BS! 5 lost part of the long arm – only one dark band
7 – monosomy 7](https://s3.amazonaws.com/brainscape-prod/system/cm/405/639/670/a_image_ios.?1668026248 “eyJvcmlnaW5hbFVybCI6Imh0dHBzOi8vczMuYW1hem9uYXdzLmNvbS9icmFpbnNjYXBlLXByb2Qvc3lzdGVtL2NtLzQwNS82MzkvNjcwL2FfaW1hZ2Vfb3JpZ2luYWwuP2JhOTc2NDdlYWY2OTMxNmM2NjdhZDVmNDE3ZTI4MWE3In0=”)
Type of molecular abnormalities with apparently normal chromosomes
point mutation
loss of tumour suppressor genes
partial duplication
cryptic deletion
depict normal granulocyte maturation
Myeloblast on L
Neutrophil on R