PBL week 3 wrap up Flashcards
what is leukaemia
usually cancers of white (immature) blood cells
most common type of cancer affecting children, 30% of all cancers
what is the most common type of leukaemia in children
acute lymphoblastic leukaemia
ALL
where do leukaemia cells normally spread to
the lymph nodes
liver
spleen
central nervous system
what early stage blood cell do stem cells make
immature blast cells
two types of stem cells that further produce blood cells
myeloid stem cell
lymphoid stem cell
lymphoblasts
give rise to T and B lymphocytes
myeloblasts
give rise to a number of white blood cells
abnormal/deregulated blasts
give rise to myeloid and lymphocytic leukaemias
acute
sudden onset
chronic
develop over time
describe how ALL develops
bone marrow makes too many lymphoid blast cells
shown in a blood test as having an abnormally high white blood cell count
these lose their ability to differentiate into normal B or T cells
levels of immature lymphoblasts build up and start to occupy space in the bone marrow
means less space for other blood cells so low number of functional or mature white and red blood cells and platelets
where else can lymphoblasts build up
other parts of the lymphatic system: spell, liver and lymph nodes
these then swell
diagnosis of ALL from blood cells
more than or equal to 20% of cells in bone marrow are blasts
normal blast levels are less than or equal to 5%
what may be associated with better prognosis
increased hyperdiploidy, more than 50 chromosomes
and the ETV6-RUNX1 (fusion gene) in children
which translocation is more prevalent in adults than children
BCR-ABL1
30% adults and 5% children
which gene marker is associated with poor prognosis
the presence of BCR-ABL1
5 year acute lymphoblastic leukaemia survival rates in England
younger patients have a significantly better survival rate but increased risk of developing secondary cancer later in life
what are the stages of ALL treatment strategy
induction
consolidation
interim maintenance
delayed intensification
maintenance
induction treatment
intensive
aimed at destroying as many leukaemia cells as possible
chemotherapy: dexamethasone, asparaginase and vincristine for 6 weeks
98% of children go into remission after 4-6 weeks of induction chemotherapy
what are the middle stages of the ALL treatment determined by
treatment response (minimum residual disease)
genetic marker (BR-ABL1), enable personalised therapeutic treatment options
maintenance therapy
mercaptopurine daily
methotrexate weekly
for three years
this removes any residual disease
reciprocal translocation
occurs between chromosomes 9 and 22
philadelphia positive
the Abl1-tyrosine kinase is under the BCR promoter
new BCR-Abl1 fusion protein
constitutively active
higher tyrosine kinase activity
BCR-Abl1 fusion gene
found in ALL but more common in chronic myeloid leukaemia CML
30% in adults, 5% children, 90% in CML
what is the function of BCR-Abl1
activates RAS signalling
increases cell proliferation
first generation of BCR-Abl kinase inhibitor and its drug resistance
called Imatinib
development of drug resistance due to:
-acitvation of alternative pathways
-over expression of MCR-Abl1
-drug efflux
-mutaitons in BCR-Abl1
new BCR-ABl1 tyrosine kinase inhibitors
inhibition of additional kinases
increased potency
maintenance of high cellular concentration
BCR-Abl1 mutant specific function
PCR
polymerase chain reaction
very sensitive and rapid to identify a specific gene
makes it possible to identify the presence of a gene from a few cells
ant look at larger changes in chromosomes
identify specific genes to plan a treatment plan
used to monitor progress of treatment
PCR use in ALL
could be used to identify if a patient has the BCR-Abl1 gene translocation
fluorescence in situ hybridisation FISH
another technique that can be used to look for changes in chromosomes and genes
uses special fluorescent dyes (probes) that attach to specific genes or parts of chromosomes
done on blood or bone marrow samples
can find chromosome changes or additional copies of genes (amplification)
the type of leukaemia will guide the choice of chromosomal changes to look for
