Genes that Predispose to Cancer Flashcards
What does Gleevec target?
BCR-ABL in chronic myeloid leukaemia
In which type of cancer is Ras commonly mutated?
Colon cancer
What treatment is available to chronic myeloid leukaemia?
Imatinib (Gleevec)
Which Cylin initiates the cell cycle?
CylinD-CDK4
Why are B cells particularly prone to developing into neoplasms?
The antibody diversification process including class switching and somatic hypermutation cause increased mutations in non-Ig genes
How does the Bcr-Abl aberration arise?
Due to a philadelphia chromosome between 9 and 22
Which lymphoid cell makes up the majority of the lymphoid neoplasms?
B-cells
What type of protein is ABL?
A kinase
Changes in which factors in CLL are associated with poor prognosis?
ZAP-70
p53
What are the six classical hallmarks of cancer?
Evasion of apoptosis
Autonomous replication
Cell immortality
Angiogenesis
Evading growth inhibitory signals
Activating invasion and metastasis
What do CylinD’s do?
Regulate the cell cycle
Why is Gleevec so well tolerated?
It only target 3 kinases (out of 90)
What is the major mechanism of CLL formation?
Loss of miRNA 15a and 16-1 regulation of Bcl-2 > loss of apoptosis
Subsequent changes in ZAP-70 and p53
Which 2 proteins mediate the miRNA silencing of mRNA?
Dicer
RISC
What does Bcl-2 control the cell?
Retention of cyt c proteins in the mitochondria to promote cell survival
What mutation leads to the development of chronic myeloid leukaemia (CML)?
Philadelphia chromosome: Bcr-Abl
Why isn’t Gleevec curative?
Because the mutated progenitor cells do not cycle often therefore are protected from Gleevec
What is the primary mutation that leads to the development of chronic lymphocytic leukaemia?
Bcl-2
Blast crisis’ occur in which type of leukaemia?
CML
How does ZAP-70 act in CLL?
Increase the pro-survival effect of Bcl-2
In which pathology are smudge cells found?
CLL
How does a mutated BCR-ABL protein cause neoplasmic transformation?
It activates proliferation, anti-apoptosis, migration and change in metabolism
How do new CLL treatments work?
ABT-199 which blocks excessively high levels of Bcl-2
What precipitates a CML blast crisis?
The acquisition of a further mutation, separate from bcr-abl, that increases its potential to cause damage
