10th March - Lymphoma/Leukaemia therapy Flashcards
What is leukaemia?
Cancer which starts in the blood forming tissue, usually the bone marrow, leading to overproduction of white blood cells
What is lymphoma?
Cancer that begins in cells of the immune system
What is the main function of lymphocytes?
Antibody production
What is Thymic stromal lymphopoeitin (TSLP)?
A four helix bundle cytokine that plays a critical role in regulation of immune response and the differentiation of hematopoeitic cells
What is the receptor for TSLP?
IL7Ralpha chain and a TSLP receptor heterdimer
Is TSLPR commonly upregulated or downregulated in cancer?
Overexpressed
How does TSLPR promote relapse of cancer?
Promotes survival in response to low levels of TSLP in bone marrow
Outline the TSLP pathway
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
What is the chromosome translocation that causes the philadelphia chromosome?
Chr22 –> Chr 9
What is the activity of BCR?
It has S/T kinase activity and is a GAP for RAC1 and CDC42
Who discovered Imatinib Mesylate?
Druker
What is Rifuxamib?
A target of CD20 which is OE in B-cell lymphomas and leukaemias
What is a common mutation for BCL-10?
translocation to chromosome 14 putting it under the control of an Ig enhancer –> inappropriate activation of NFkB target genes
What is hairy cell leukaemia?
A very rare form of B-cell lymphoma in which there is a B-Raf V600E mutation
What is targeted by Idelasib?
PI3K delta
How does BTK cause cancer?
It is a tyrosine protein kinase which activates Akt and mTOR
Leads to B-cell activation
Promotes adhesion and migration through integrins
What does Ibnitib inhibit?
BTK
What do BCL2 inhibitors cause?
Apoptotic death by increasing mitochondrial outer membrane permeability
What is ABT-199?
A potent and selective inhibitor for BCL-2
What is the graft vs tumour effect?
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
What is the Graft vs host effect?
A medical complication following the receipt of transplanted tissue from a genetically different person
What would be one method of recovering immune response against tumour?
Reprogramming T cells to identify and eliminate malignant cells through tumour specific antigen recognition
Outline how T-cells can be reprogrammed to target tumours
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
