Flashcards in BC - L3 Deck (22)
hallmarks of cancer
cancers of B cells
chromosomal translocation cancers
types of B Cell cancers
classification of B cell malignancies
evading growth suppression
metastasis – dissemination
immortality of replication (senescence)
blocking apoptosis (cell death)
Two dangerous processes of being a B cell?
Chromosomal translocation cancers?
cell cycle and growth regulators
cell survival proteins
DNA damage sensors
drivers: cyclins - activate CDKs
brakes: bind specific CDKs
transcription factor with wide influence
regulates cell growth
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)
DNA damage goes unchecked
a malignancy of lymphocytes
HL - Reed-Sternberg cell
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
cancer of plasma cells
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?
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?
B cell leukaemia & lymphoma
Drugs targeting survival
Treatment of NHL?
antibody Rituximab (R-CHOP)
3-8 cycles, 3 weeks each
bone marrow transplantation
addresses the nature of the cell (not rapidly accumulating, gradual proliferation)
Bortezimib - inhibits 26S proteasome
leukaemia & lymphoma treatments?
Rituximab (anti-CD20 antibody)
all mature B cells express CD20 (not plasma)
treatments for specific subtypes of DLBCL?
used to suggest different drugs:
low risk - RCHOP
high risk - specific enzyme inhibitors