MISC Flashcards
Describe the normal cell cycle using a detailed
annotated diagram [2 for diagram + 4 for annotations]
At both checkpoints, if DNA is not satisfactory for the
next phase, DNA repair takes place OR apoptosis occurs
Name the most important protein involved with cell
cycle regulation at the G1/S checkpoint (½)
p53
Outline three (3) molecular mechanisms whereby haematologic malignancies may develop (3) (Super NB)
- Gain of function of proto-oncogenes
- Mutations in tumour suppressor genes
- Defects in apoptotic pathway, so cells do not die but accumulate
List four (4) genetic mechanisms which may underlie haematologic malignancies (4 x ½ = 2)
Point mutations,
Translocations, Chromosomal deletions, Chromosomal duplications,
DNA methylation/ histone deacetylation
Outline three attributes/characteristics of tumour suppressor genes (3)
Responsible for protecting the organism against malignancy & regulating
the cell cycle. Loss of normal tumour suppressor gene function occurs due to loss of function mutations (point mutation/ deletion) and this may lead development of malignancy. TP53 is the most significant tumour suppressor gene in human cancer and is mutated or inactivated in >50% of malignancies.
Define proto-oncogenes and outline their functions (3) (Super NB)
Normal genes that code for proteins which are involved in the regulation of cell growth, proliferation and differentiation.
Outline how a proto-oncogene may be involved in leukaemogenesis (2) (NB)
Malignancy arises as a result of change of structure/gain-of function of a proto-oncogene into an oncogene leading to uncontrolled proliferation.
Leukaemia may arise as a result of alterations in oncogenes. Outline three (3) molecular mechanisms whereby loss of function of oncogenes may occur (4½) (NB)
Large deletions with deletion of oncogene
Small deletions of only a few bases, causing frame shift and production of a different protein.
Mutations that result in STOP codons so protein not produced
Mutations in promoter sequence of gene that cause decreased gene expression.
Mutations in splice regions of gene, with aberrant mRNA splicing decreased synthesis of protein.
The high proliferation rate of cells in acute leukaemia is thought to be the result of the unregulated activity of oncogenes. Describe the mechanisms that may result in gain of function of oncogenes (4) (Super NB)
“Gain of function” of an oncogene may result from:
Amplification of the gene so that several copies of the gene occur.
Mutation of the gene – especially at sites which are important for regulation of gene function so that mutated gene is no longer responsive to normal control mechanisms.
Mutation of the regulators of the oncogene
Translocations with exchange of material between chromosomes which results in two situations
o Production of a fusion gene – part of oncogene is attached to another gene. This interferes with its function and susceptibility to regulatory control mechanisms.
o Transfer of the oncogene to a site which is actively transcribed. E.g. In many B lymphoid malignancies, translocations occur which move oncogenes to sites of immunoglobulin gene loci, which are actively transcribed, and so the translocated gene falls under the influence of these mechanisms.
Define apoptosis (1)
The regulated process (½) of physiological cell death (½)
Name and briefly describe two (2) cellular pathways leading to apoptosis (2x2 = 4)
Any two of:
Receptor-mediated pathway (½): Binding to the FAS/TNF receptor (½) on a target cell triggers the intracellular release of caspases (½) via activation of an intracellular death domain (½).
Mitochondrial pathway (½): Damage to the cell triggers release of cytochrome C (½) from mitochondria which activates caspases (½). BCL proteins (½) regulate the mitochondrial membranes
p53 pathway (½): p53 activates apoptosis by raising the level of BAX (½) which increases cytochrome C release (½) and shuts down the cell cycle to stop division (½)
Leukaemia may be associated with decreased rates of apoptosis. Outline the two (2) main mechanisms of activation of apoptosis in normal cells (3+3 = 6) (NB)
Receptor mediated pathway: A “death receptor” (e.g. tumour necrosis factor receptor) on the cell surface binds to its ligand and this triggers the activation of caspases which cause DNA digestion and disintegration of the cell skeleton.
If irreparable damage to cellular constituents (e.g. DNA) is detected, the mitochondria are triggered to release cytochrome c which causes activation of caspases and hence apoptosis.
List four (4) cellular events that occur after the activation of apoptosis by the pathways discussed above (½x4 = 2)
Cellular shrinkage, Cleavage of DNA, Condensation of nuclear chromatin, Condensation of cytoplasm, Nuclear fragmentation, Phagocytosis of apoptotic bodies by macrophages
Give an example of how a genetic event leads to the dysregulation of apoptosis and a haematological malignancy (4x½ = 2)
Any four including: t(14;18) translocation (½) in Follicular lymphoma (½) leads to the over expression of BCL2 (½). This reduces apoptosis (½) and causes the accumulation (½) of malignant cells.
Outline two (2) properties/ characteristic features of stem cells (2) (NB)
Self-renewal: Ability divide and replicate themselves to produce more stem cells
Multi-potentiality/ Differentiation: Ability to proliferate and undergo differentiation to more specialized cell types
