17. Mature B-cell neoplasms Flashcards
What is the difference between CLL and SLL?
Same disease but…
Chronic Lymphocytic Leukaemia - abnormal lymphocytes in blood
Small Lymphocytic Lymphoma - abnormal lymphocytes in lymph nodes
How is CLL characterised at the cellular level?
Accumulation of mature B cell lymphocytes in blood, BM, spleen, lymph nodes
CD5+
Which cytogenetic techniques are used in the diagnosis of CLL and why?
Karyotyping is limited due to low mitotic activity of leukaemic cells in vitro - may miss clonal chromosomal abnormalities
FISH on uncultured interphase cells - identify abnormality in larger proportion of CLL cases (80% vs 50%)
What are the most common chromosomal abnormalities in CLL?
What are the prognoses?
Deletion 17p (TP53) - poor
Deletion 11q (ATM) - poor
Deletion 13q14 - favourable
Trisomy 12 - intermediate
What molecular testing is required in CLL?
TP53
IGVH somatic hypermutation analysis
What prognoses are associated with IGHV SHM?
Mutated IGHV = less aggressive, longer time to first treatment
Un-mutated IGHV = more aggressive, earlier TTFT
What is the purpose of VDJ rearrangments?
Part of adaptive immunity
Rearrangments of VDJ segments in immunogloblin heavy chain form repetoire of unique antibodies (immunogloblin) needed for immunity
What are the VDJ regions?
Regions of the immunogloblin heavy gene loci
Variable (66, 44 functional)
Diversity (27)
Joining (6)
What is the purpose of somatic IGH hypermutation?
Takes places after VDJ recombination
Adds/deletes nucleotides - adds to the number of unique immunoglobins needed for immunity
How is IGH hypermutation tested for?
Sanger sequencing
F primers 5’ of each of the 7 different V families
Common R primer (JHCONS) binds to homologous region 3’ of each J segment
Sequence data uploaded to IMGT/ARREST - determine which V, D, J segments are present
Sequence compared to germline to determine mutation level
Which V family segments are most frequently used?
V3
V4
V1
What constitues a mutated and unmutated result?
Unmutated = >98% similarity to germline sequence
Mutated = <98
What information does IGH sequencing give, other than % simililarity?
19 defined stereotypes in CLL, 4 provide prognostic info:
1 - aggressive disease
2 - poor prognosis regardless of mutation status
3 - indolent CLL, good prognosis
4 - aggressive, risk of Richter’s transformation (into DLCBL)
What is the phenotype of CLL?
Often asymptomatic at diagnosis
Fatigue, haemolytic anaemia, splenomegaly
High inherited predisposition
What is the course of disease in CLL?
Highly variable
Near normal life expectancy to rapid progression & early death
