BC - L3 Flashcards
Topics?
hallmarks of cancer cancers of B cells chromosomal translocation cancers types of B Cell cancers classification of B cell malignancies therapies
hallmarks?
sustaining proliferation evading growth suppression metastasis – dissemination immortality of replication (senescence) blood supply blocking apoptosis (cell death)
Two dangerous processes of being a B cell?
CSR
SHM
Chromosomal translocation cancers?
cell cycle and growth regulators
cell survival proteins
DNA damage sensors
Growth regulators?
drivers: cyclins - activate CDKs
brakes: bind specific CDKs
myc
myc?
transcription factor with wide influence
drives proliferation
regulates cell growth
inhibits differentiation
Cell survival proteins?
BH3-only - killers
Bcl2 - protectors
Describe the apoptosis pathway
-
DNA damage sensors?
Bcl6 - transcriptional repressor
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)
Bcl6 mutations?
DLBCL
DNA damage goes unchecked
Lymphoma?
a malignancy of lymphocytes
HL - Reed-Sternberg cell
NHL
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
Multiple myeloma?
cancer of plasma cells
MGUS
in bone marrow - osteoporosis
Diagnosis of myeloma?
monoclonal antibody in serum (paraprotein, Bence Jones proteins free light chains)
clonal plasma cells on bone marrow biopsy
end organ damage
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
Areas of therapies looked at?
NHL MM B cell leukaemia & lymphoma DLBCL Drugs targeting survival
Treatment of NHL?
chemotherapy (CHOP) antibody Rituximab (R-CHOP) 3-8 cycles, 3 weeks each radiation bone marrow transplantation
MM treatment?
addresses the nature of the cell (not rapidly accumulating, gradual proliferation)
Bortezimib - inhibits 26S proteasome
bisphosphonates
leukaemia & lymphoma treatments?
Rituximab (anti-CD20 antibody)
all mature B cells express CD20 (not plasma)
treatments for specific subtypes of DLBCL?
two types: GC AB used to suggest different drugs: low risk - RCHOP high risk - specific enzyme inhibitors
Drugs targeting survival?
ABT-263 - blocks binding site of Bcl-2, therefore releasing death inducer BH3
CLL patients respond to treatment with BH3 mimetic ABT-199
B cell cancers & chronic signalling from the B cell receptor
