Flashcards in BC - L3 Deck (22):
1
Topics?
hallmarks of cancer
cancers of B cells
chromosomal translocation cancers
types of B Cell cancers
classification of B cell malignancies
therapies
2
hallmarks?
sustaining proliferation
evading growth suppression
metastasis – dissemination
immortality of replication (senescence)
blood supply
blocking apoptosis (cell death)
3
Two dangerous processes of being a B cell?
CSR
SHM
4
Chromosomal translocation cancers?
cell cycle and growth regulators
cell survival proteins
DNA damage sensors
5
Growth regulators?
drivers: cyclins - activate CDKs
brakes: bind specific CDKs
myc
6
myc?
transcription factor with wide influence
drives proliferation
regulates cell growth
inhibits differentiation
7
Cell survival proteins?
BH3-only - killers
Bcl2 - protectors
8
Describe the apoptosis pathway
-
9
DNA damage sensors?
Bcl6 - transcriptional repressor
10
Bcl6 normal function?
required for GC to form
inhibits B cell differentiation during GC to enable CSR & affinity maturation
blocks DNA damage response (represses p53)
11
Bcl6 mutations?
DLBCL
DNA damage goes unchecked
12
Lymphoma?
a malignancy of lymphocytes
HL - Reed-Sternberg cell
NHL
13
Leukaemia?
cancer that starts in blood forming tissue such as bone marrow and causes large numbers of malignant cells to be produced and enter the bloodstream
ALL
CLL
14
Multiple myeloma?
cancer of plasma cells
MGUS
in bone marrow - osteoporosis
15
Diagnosis of myeloma?
monoclonal antibody in serum (paraprotein, Bence Jones proteins free light chains)
clonal plasma cells on bone marrow biopsy
end organ damage
16
Classification of B cell malignancies?
patient’s condition
histology of tumour or involved tissues (including blood)
karyotype of tumour cells – chromosome number and structure
abnormal accumulation of clones of cells
more recently, flow cytometry (way of looking at proteins on surface on cancer cells) using mAbs that recognise surface molecules (CDs) on malignant cells
17
Areas of therapies looked at?
NHL
MM
B cell leukaemia & lymphoma
DLBCL
Drugs targeting survival
18
Treatment of NHL?
chemotherapy (CHOP)
antibody Rituximab (R-CHOP)
3-8 cycles, 3 weeks each
radiation
bone marrow transplantation
19
MM treatment?
addresses the nature of the cell (not rapidly accumulating, gradual proliferation)
Bortezimib - inhibits 26S proteasome
bisphosphonates
20
leukaemia & lymphoma treatments?
Rituximab (anti-CD20 antibody)
all mature B cells express CD20 (not plasma)
21
treatments for specific subtypes of DLBCL?
two types:
GC
AB
used to suggest different drugs:
low risk - RCHOP
high risk - specific enzyme inhibitors
22