Lec 13 - Malignancy Flashcards
what is a haem malignancy
a clonal disease when a cell has undergone fneetic changes leading to excessive prlofieration and/or resistance to apotosis
what are clonal diseases derived from
a single cell that has undergone genetic alteration
genereal causes fo malignancy
usually combo of genetic prdisposition and environemtnl factors:
- infection
- ionising radiation
- chemicals
- drugs
example of genetic predisposition
downs syndrome = increased risk of leukemia
2 viruses that can cause malignancy
- human T-lymphotropic virus type 1 (HTLV-1) = adult t cell leukemia/lymphoma
- EBV= Burkitts lymphoma
cause of acute lymphoblastic leukaemia
- mutation in utero
- but 2nd post birth event necassary for it to occur (mech unclear
ALL: diff between incidence in kids that attend daycare and that dont
if do = less likely = more exposure to common diseases, devleoped immune system
example of ionising radiation causing alignancy
hiroshima and nagasaki = in risk of malignancy
what chemicals can cause inc risk of malignancy
benzene (chronic exposure)
drugs that inc risk of malignancy
alkylating agents
can cause myeloid leukemia
what are oncogenes derived from
proto-oncogenes
what type of gain of function mutations may a proto oncogene get to turn into an oncogene
- amplification
- point mutations
- chromosomal translocation
3 effects of oncogenes
- uncontrolled prolfieration
- blockage of differentiation
- preventing apoptosis
what type of mutation usually inactivates a tumour suppressor gene
loss of function mutation
msot significant TSG in human cancer
P53
genetic abnormalities associated w haematological malignancy
Point mutations
Gene and chromosomal deletions
Chromosomal duplication (e.g. trisomy 12 in CLL) or gene amplification (not common)
3 reasons for detecting genetic markers in haematological malignancy
- initial diagnosis and subclassification
- treatment
- monitoring minimal residual disease
what is minimal residual disease (MRD)
lowest number of malignant cells detectable using available methods
before treatment, avg MRD
10^13-10^14 cells
def of remission
when less than 5% of blasts are detected in marrow
so = below detection limits of conventional techniques
what is PCR capable of detecting
1 malignant cell in up to 10^6 normal cells
= very specific
when is risk of relapse low
when MRD is not detected
so can then potentially reduce treatment
karyotype analysis
morphological analysis of chromosomes from tumour cells
fluorescent in situ hybridisation
more sensitive than karyotype analysis
- binds to specific parts of genome
=
- detects extra copies of genetic material in case of duplication
and
- translocations (importnant in determining the subclassification)
