Leukaemia

Question 1

What was the incidence of leukaemia in 2010?

Answer 1

8,257 new cases (4816 male, 3441 female)

Question 2

Since the 1970s has the mortality rate of leukaemia been increasing or decreasing?

Answer 2

The mortality rate is decreasing, consequently the prevalence is increasing.

Question 3

Which two types of chromosomal translocation cause leukaemia?

Answer 3

1. Placing a strong regulatory element upstream of an oncogene, causing its over-expression.
2. An inframe fusion event that creates a novel and/or dysfunctional protein.

Question 4

What are the main symptoms of AML?

Answer 4

Bruising
Bleeding gums
Shortness of breath

Question 5

What is the treatment for AML?

Answer 5

Chemotherapy

Question 6

What is AML?

Answer 6

Accumulation of immune myeloid cells (blasts), proliferating in bone marrow.

Question 7

Give 3 commonly mutated genes in AML.

Answer 7

CD117/c-kit
Runx1
CD135/FLT3

Question 8

Give 4 common chromosomal abnormalities in AML.

Answer 8

t(8;21) - Runx1 (AML1-ETO fusion protein)
Inv16 - Core binding factor β subunit
t(15;17) - Retinoic acid receptor α subunit
t(9;11) - MLLT3-MLL

Question 9

What is Runx1?

Answer 9

A transcription factor

Question 10

What does Runx1 form a complex with?

Answer 10

Core binding factor.

Question 11

Which protein causes DNA binding of Runx1 to increase 10-fold?

Answer 11

CBFβ

Question 12

What does AML1-ETO impede?

Answer 12

Myeloid differentiation.

Question 13

What is the most common paediatric malignancy?

Answer 13

ALL

Question 14

What is the peak age range for ALL?

Answer 14

2-5 years old

Question 15

What is the treatment for ALL?

Answer 15

Chemotherapy, radiotherapy, stem cell transplant

Question 16

What percentage of paediatric patients are cured (5 year survival)?

Answer 16

Approximately 95%

Question 17

What fraction of adult cases show post-5 survival?

Answer 17

1/3

Question 18

What are common chromosomal translocations in ALL?

Answer 18

t(8;14)
t(9;22)
t(1;19)
t(12;21)

Question 19

What is the most common chromosomal translocation in ALL?

Answer 19

T(12;21) TEL-AML1 ( >25%)

Question 20

Which virus could cause overproduction of myc in ALL?

Answer 20

Epstein Barr Virus

Question 21

What happens in t(8;14) translocation?

Answer 21

Myc moves to regulatory element of Eμ, this drives over-expressions expression of myc.

Question 22

Which translocation is the Philadelphia chromosome?

Answer 22

t(9;22)

Question 23

Which fusion protein does t(9;22) give rise to?

Answer 23

bcr/abl

Question 24

What does bcr/abl create?

Answer 24

A novel protein tyrosine kinase (PTK)

Question 25

Which pathway is the abl PTK linked to?

Answer 25

ras/MAP kinase pathway

Question 26

What does the ras/MAP kinase pathway regulate?

Answer 26

Cell proliferation

Question 27

Which kinase family is abl a member of?

Answer 27

Src

Question 28

The TEL-AML1 fusion protein's pattern of interaction with transcriptional modifiers is dramatically altered. What does this change?

Answer 28

The spectrum of genes targetted and expressed.

Question 29

Which ALL translocation occurs in utero?

Answer 29

t(12;21)

Question 30

What are the TEL and AML genes transcriptional regulators for?

Answer 30

Haematopoeisis

Question 31

What needs to occur for a child with a TEL/AML translocation to develop leukaemia?

Answer 31

The second normal TEL gene is lost.

Question 32

Which environmental factors lead to loss of TEL?

Answer 32

Viruses, radiation, immunodeficiency, chemicals

Question 33

What is the most common geriatric malignancy in the West?

Answer 33

Chronic Lymphocytic Leukaemia (CLL)

Question 34

Which cells are affected in CLL?

Answer 34

BcR+

Question 35

Name 4 commonly mutated genes in CLL.

Answer 35

Notch1 p53 MyD88 ATM

Question 36

How can CLL be treated?

Answer 36

Incurable, younger patients can get stem cell transplants.

Question 37

What are the two forms of CLL?

Answer 37

Indolent - patients don't know they have it. | Aggressive - poor 5 year survival.

Question 38

What effect does IgVH status have on CLL prognosis?

Answer 38

Unmutated VH genes (>98% identity with germline sequence) are at elevated risk of poor prognosis. Mutated VH genes have better prognosis.

Question 39

What is Zap-70 and how does it affect CLL prognosis?

Answer 39

A tyrosine kinase normally associated with TcR. High level of Zap-70 correlates with CLL progression and a poor outcome.

Question 40

What plasma concentration of sCD23 suggests poor prognosis for CLL patients?

Answer 40

>60ng/ml

Question 41

How do telomeres affect CLL prognosis?

Answer 41

Shortened telomeres - poor prognosis. | Telomeres are a very good indicator of prognosis