10th March - Lymphoma/Leukaemia therapy

Question 1

What is leukaemia?

Answer 1

Cancer which starts in the blood forming tissue, usually the bone marrow, leading to overproduction of white blood cells

Question 2

What is lymphoma?

Answer 2

Cancer that begins in cells of the immune system

Question 3

What is the main function of lymphocytes?

Answer 3

Antibody production

Question 4

What is Thymic stromal lymphopoeitin (TSLP)?

Answer 4

A four helix bundle cytokine that plays a critical role in regulation of immune response and the differentiation of hematopoeitic cells

Question 5

What is the receptor for TSLP?

Answer 5

IL7Ralpha chain and a TSLP receptor heterdimer

Question 6

Is TSLPR commonly upregulated or downregulated in cancer?

Answer 6

Overexpressed

Question 7

How does TSLPR promote relapse of cancer?

Answer 7

Promotes survival in response to low levels of TSLP in bone marrow

Question 8

Outline the TSLP pathway

Answer 8

TSLP binds to TSLPR –> JAK1 –> PI3K –> AKT –> mTCH –> S6 –> Cell proliferation and cell survival
TSLP binds to TSLR –> JAK2 –> STAT5 A/B –> Cell proliferation and cell survival

Question 9

What is the chromosome translocation that causes the philadelphia chromosome?

Answer 9

Chr22 –> Chr 9

Question 10

What is the activity of BCR?

Answer 10

It has S/T kinase activity and is a GAP for RAC1 and CDC42

Question 11

Who discovered Imatinib Mesylate?

Answer 11

Druker

Question 12

What is Rifuxamib?

Answer 12

A target of CD20 which is OE in B-cell lymphomas and leukaemias

Question 13

What is a common mutation for BCL-10?

Answer 13

translocation to chromosome 14 putting it under the control of an Ig enhancer –> inappropriate activation of NFkB target genes

Question 14

What is hairy cell leukaemia?

Answer 14

A very rare form of B-cell lymphoma in which there is a B-Raf V600E mutation

Question 15

What is targeted by Idelasib?

Answer 15

PI3K delta

Question 16

How does BTK cause cancer?

Answer 16

It is a tyrosine protein kinase which activates Akt and mTOR
Leads to B-cell activation
Promotes adhesion and migration through integrins

Question 17

What does Ibnitib inhibit?

Answer 17

BTK

Question 18

What do BCL2 inhibitors cause?

Answer 18

Apoptotic death by increasing mitochondrial outer membrane permeability

Question 19

What is ABT-199?

Answer 19

A potent and selective inhibitor for BCL-2

Question 20

What is the graft vs tumour effect?

Answer 20

A graft contains donor T cells and therefore can eliminate malignant cells as the hosts T cells have been programmed not to attack the tumour

Question 21

What is the Graft vs host effect?

Answer 21

A medical complication following the receipt of transplanted tissue from a genetically different person

Question 22

What would be one method of recovering immune response against tumour?

Answer 22

Reprogramming T cells to identify and eliminate malignant cells through tumour specific antigen recognition

Question 23

Outline how T-cells can be reprogrammed to target tumours

Answer 23

Engineering T cells the express chimeric antigen receptors that link an extracellular antigen recognition domain derived from a monoclonal tumour antibody fragment to intracellular signalling domains of the T-cell receptor complex