BC - L3

Question 1

Topics?

Answer 1

hallmarks of cancer
cancers of B cells
chromosomal translocation cancers
types of B Cell cancers
classification of B cell malignancies
therapies

Question 2

hallmarks?

Answer 2

sustaining proliferation
evading growth suppression
metastasis – dissemination
immortality of replication (senescence)
blood supply
blocking apoptosis (cell death)

Question 3

Two dangerous processes of being a B cell?

Answer 3

CSR

SHM

Question 4

Chromosomal translocation cancers?

Answer 4

cell cycle and growth regulators
cell survival proteins
DNA damage sensors

Question 5

Growth regulators?

Answer 5

drivers: cyclins - activate CDKs
brakes: bind specific CDKs
myc

Question 6

myc?

Answer 6

transcription factor with wide influence
drives proliferation
regulates cell growth
inhibits differentiation

Question 7

Cell survival proteins?

Answer 7

BH3-only - killers

Bcl2 - protectors

Question 8

Describe the apoptosis pathway

Answer 8

-

Question 9

DNA damage sensors?

Answer 9

Bcl6 - transcriptional repressor

Question 10

Bcl6 normal function?

Answer 10

required for GC to form
inhibits B cell differentiation during GC to enable CSR & affinity maturation
blocks DNA damage response (represses p53)

Question 11

Bcl6 mutations?

Answer 11

DLBCL

DNA damage goes unchecked

Question 12

Lymphoma?

Answer 12

a malignancy of lymphocytes
HL - Reed-Sternberg cell
NHL

Question 13

Leukaemia?

Answer 13

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

Question 14

Multiple myeloma?

Answer 14

cancer of plasma cells
MGUS
in bone marrow - osteoporosis

Question 15

Diagnosis of myeloma?

Answer 15

monoclonal antibody in serum (paraprotein, Bence Jones proteins free light chains)
clonal plasma cells on bone marrow biopsy
end organ damage

Question 16

Classification of B cell malignancies?

Answer 16

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

Question 17

Areas of therapies looked at?

Answer 17

NHL
MM
B cell leukaemia & lymphoma
DLBCL
Drugs targeting survival

Question 18

Treatment of NHL?

Answer 18

chemotherapy (CHOP)
antibody Rituximab (R-CHOP)
3-8 cycles, 3 weeks each
radiation
bone marrow transplantation

Question 19

MM treatment?

Answer 19

addresses the nature of the cell (not rapidly accumulating, gradual proliferation)
Bortezimib - inhibits 26S proteasome
bisphosphonates

Question 20

leukaemia & lymphoma treatments?

Answer 20

Rituximab (anti-CD20 antibody)

all mature B cells express CD20 (not plasma)

Question 21

treatments for specific subtypes of DLBCL?

Answer 21

two types:
GC
AB
used to suggest different drugs:
low risk - RCHOP
high risk - specific enzyme inhibitors

Question 22

Drugs targeting survival?

Answer 22

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