Wnt/Beta-catenin Signalling In Leukaemogenesis Flashcards
What does Wnt sigalling increase
Increases c-myc
Increases cyclin D1
Increases Survivin
What are Wnt Receptors
Fiz receptors
When are Wnt receptors expressed
Expressed in early haematopoietic development and promotes stem cell self renewal
What is a Wnt inhibitor
DKK1
WHat is the role of Wnt in lymphopoiesis
Involved in the double negative stages of T cell development
What is the role of Wnt in monocyte Development
Beta catenin represses Erg2 which is required for monopoiesis
When is beta-catenin overexpressed, (What cancer)
AML
How can translocations in AML increase beta-catenin expression
PML-RAR and RUNX1-ETO
Both increases gamma catenin which can then stabilise beta-catenin
What mutation is common in AML that are karytotypically normal
FLT3 mutations
What mutations occur in FLT3 in AML
Tandem duplications
Point mutation at D836 and I36
What does FLT3 signalling activate
D*36 and I36
How is beta-catenin required for the emergence of LSC in AML
Beta-catenin is needed along with the expression of HOXA9 and MEIS1a to transform myeloid progenitor cells into AML
How dose bcr-abl affect beta catenin
Phosphorylates beta catenin at Tyr 65/87 preventing its degradation
What are the therapeutic approaches to target Wnt/Beta-catenin signalling
1) Interfere with beta catenin signalling
2) Porcupiine inhibitors)
3) tankyrase inhibitors
4) Frizzled AB/inhibitors
5) Disheveled inhibitors
How can AML affect c-myc
Translocation can increase c-myc and cause transfofrmation and proliferation
AML Cells have been shown to be intrinsically resisticant to c-myc induced apoptosis
