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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

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