PBL week 3 wrap up

Question 1

what is leukaemia

Answer 1

usually cancers of white (immature) blood cells
most common type of cancer affecting children, 30% of all cancers

Question 2

what is the most common type of leukaemia in children

Answer 2

acute lymphoblastic leukaemia
ALL

Question 3

where do leukaemia cells normally spread to

Answer 3

the lymph nodes
liver
spleen
central nervous system

Question 4

what early stage blood cell do stem cells make

Answer 4

immature blast cells

Question 5

two types of stem cells that further produce blood cells

Answer 5

myeloid stem cell
lymphoid stem cell

Question 6

lymphoblasts

Answer 6

give rise to T and B lymphocytes

Question 7

myeloblasts

Answer 7

give rise to a number of white blood cells

Question 8

abnormal/deregulated blasts

Answer 8

give rise to myeloid and lymphocytic leukaemias

Question 9

acute

Answer 9

sudden onset

Question 10

chronic

Answer 10

develop over time

Question 11

describe how ALL develops

Answer 11

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

Question 12

where else can lymphoblasts build up

Answer 12

other parts of the lymphatic system: spell, liver and lymph nodes
these then swell

Question 13

diagnosis of ALL from blood cells

Answer 13

more than or equal to 20% of cells in bone marrow are blasts
normal blast levels are less than or equal to 5%

Question 14

what may be associated with better prognosis

Answer 14

increased hyperdiploidy, more than 50 chromosomes
and the ETV6-RUNX1 (fusion gene) in children

Question 15

which translocation is more prevalent in adults than children

Answer 15

BCR-ABL1
30% adults and 5% children

Question 16

which gene marker is associated with poor prognosis

Answer 16

the presence of BCR-ABL1

Question 17

5 year acute lymphoblastic leukaemia survival rates in England

Answer 17

younger patients have a significantly better survival rate but increased risk of developing secondary cancer later in life

Question 18

what are the stages of ALL treatment strategy

Answer 18

induction
consolidation
interim maintenance
delayed intensification
maintenance

Question 19

induction treatment

Answer 19

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

Question 20

what are the middle stages of the ALL treatment determined by

Answer 20

treatment response (minimum residual disease)
genetic marker (BR-ABL1), enable personalised therapeutic treatment options

Question 21

maintenance therapy

Answer 21

mercaptopurine daily
methotrexate weekly
for three years

this removes any residual disease

Question 22

reciprocal translocation

Answer 22

occurs between chromosomes 9 and 22
philadelphia positive
the Abl1-tyrosine kinase is under the BCR promoter

Question 23

new BCR-Abl1 fusion protein

Answer 23

constitutively active
higher tyrosine kinase activity

Question 24

BCR-Abl1 fusion gene

Answer 24

found in ALL but more common in chronic myeloid leukaemia CML
30% in adults, 5% children, 90% in CML

Question 25

what is the function of BCR-Abl1

Answer 25

activates RAS signalling
increases cell proliferation

Question 26

first generation of BCR-Abl kinase inhibitor and its drug resistance

Answer 26

called Imatinib
development of drug resistance due to:
-acitvation of alternative pathways
-over expression of MCR-Abl1
-drug efflux
-mutaitons in BCR-Abl1

Question 27

new BCR-ABl1 tyrosine kinase inhibitors

Answer 27

inhibition of additional kinases
increased potency
maintenance of high cellular concentration
BCR-Abl1 mutant specific function

Question 28

PCR

Answer 28

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

Question 29

PCR use in ALL

Answer 29

could be used to identify if a patient has the BCR-Abl1 gene translocation

Question 30

fluorescence in situ hybridisation FISH

Answer 30

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