Leukaemia

Question 1

What is principle site of blood cell formation?

Answer 1

The bone marrow

Question 2

What is the average lifespand of a RBC?

Answer 2

100 days

Question 3

What is Leukaemia?

Answer 3

It is cancer of the blood.

Question 4

What are the symptoms of Leukaemia?

Answer 4

• Reduced platelets - Abnormal bruising/bleeding
• Suppressed/dysfunctional white cells - increased risk of infection
• RBC deficiency - anaemia, shortness of breath and fatigue

Question 5

What are the four classes of Leukaemia?

Answer 5

ALL - Acute Lymphocytic Leukaemia

AML - Acute Myelogenous Leukaemia

CLL - Chronic Lymphocytic Leukaemia

CML - Chronic Myelogenous Leukaemia

Question 6

What two lineages can leukaemias arise from?

Answer 6

Myeloid - Eosinophils, Basophils, Neutrophils, Monocytes, Platelets, RBC

Lymphoid - T and B cells

Question 7

What is the origin of most Leukaemias in children?

Answer 7

Acute Lymphoid

80% are ALL, 20% AML

Question 8

Which lineage do most leukaemias in children orginate from?

Answer 8

The B-cell lineage

Question 9

What percentage of acute leukaemias are involved in chromosomal translocations?

Answer 9

65%

Question 10

What is a driving force in a large proportion of acute leukaemias?

Answer 10

65% of acute leukaemias involve chromosomal translocations.

Question 11

What are the most frequent targets of chromosomal translocations in acute leukaemias?

Answer 11

Transcription factors or components of signalling pathways

This results in either

• the inappropriate expression of a gene in the wrong cell
• expression of a novel gene

Question 12

What are the two primary functions of the blood system?

Answer 12

To carry oxygen around the body

Immune system

Question 13

What is the difference between acute and chronic tumours?

Answer 13

Acute tumours develop very rapidly

Chronic tumours develop over a long time

Question 14

What is the Philadelphia chromosome?

Answer 14

It is found in almost all cases of chronic myeloid leukaemia.

Almost always a key step in this particular type of leukaemia.

It was discovered in Philadelphia.

P chromosome is a tiny fragment. Reciprocal translocation between Ch9 and Ch22. This swap results in a slightly bigger Ch9 and a tiny Ch22.

The Philadelphia Ch is the tiny Ch22.

Question 15

What are the two genes that are involved in the formation of the Philadelphia chromosome?

Answer 15

abl and bcr genes.

The position of break in the bcr gene is variable.

Question 16

What two chromosome join and translocate to form the Philadelphia chromosome?

Answer 16

Chromosome 9

Chromsome 22

Question 17

What is the oncogenic product of the fusion event between Ch9 and Ch22?

Answer 17

Hybrid Bcr-Abl protein

Question 18

What arises from the translocation between ablandbcr?

Answer 18

A hybrid Bcr-Abl protein that acts as a constitutively activated tyrosine kinase.

It phosphorylates targets inappropriately, this triggers oncogenic events.

Question 19

What pathways does bcr/abl fusion activate?

Answer 19

Ras pathway

PI3K pathway

Jak-STAT pathway

Question 20

What transcription factors are affected by bcr/abl fusion?

Answer 20

bcr/abl fusion can activate transcription factors including Jun, Myc and NF-KB.

Question 21

How many break points are there in bcr?

Answer 21

Three

These can produce three different fusion proteins depending on where the break occurs.

ALL Acute Lymphoblastic Leukaemia

CML Chronic Myelogenous Leukaemia

CNL Chronic Neutrophili Leukaemia

Question 22

Why do leukaemias exhibit specific translocations?

Answer 22

Either…

Translocations are random, and the effect of some can be selected for in the expansion of clones

OR

Translocations are non-random and some cause clonal expansion

Question 23

In blood cells what machinery binds

Answer 23

There is a higher frequency of DNA recombination in the blood