Leukaemia

Question 1

What is Leukaemia and what is it a result of?

Answer 1

Leukaemia is a type of cancer. It is the result of a mutation in a precursor of a myeloid or lymphoid cell which gives rise to a clone that steadily creates normal cells.

Question 2

How can we describe the origin of the Leukaemia?

Answer 2

Myeloid or lymphoid

Question 3

What is the main way in which Leukaemia differs from other cancers?

Answer 3

The cancerous cells flow in the bloodstream so they are mobile rather than being a solid tissue. This makes it hard to apply the normal concepts of local invasion to neighbouring cells.

Question 4

What two terms do we use instead of malignant and benign for leukaemia?

Answer 4

While not entirely accurate, we can use the terms acute or chronic to show malignancy.

Question 5

What are the consequences of acute leukaemia?

Answer 5

Acute leukaemia, if untreated, has profound pathological effects and leads to death in a matter of days, weeks or months.

Question 6

What are the consequences of chronic leukaemia?

Answer 6

Chronic leukaemia , if untreated, causes less impairment of function of normal tissues and although it will eventually lead to death, this usually doesn’t occur for a number of years.

Question 7

What are the 4 main ways we can describe leukaemia?

Answer 7

Myeloid or lymphoid.

Acute or chronic.

Question 8

How can we describe mutations in germ cells?

Answer 8

We can describe them as beneficial, neutral or harmful.

Question 9

What do beneficial mutations allow?

Answer 9

They permit a species to evolve. While they tend to be quite rare, with many more neutral or harmful mutations occurring, it is the trade-off we take in order to allow ourselves to evolve.

Question 10

What can cause a mutation in a somatic cell?

Answer 10

Exposure to mutagens or a random spontaneous process.

Question 11

Why might age be a factor in increasing the likelihood of mutation?

Answer 11

The older someone is, the more likely it is that enough spontaneous or induced mutations have accumulated in a single cell for the cell to expand into a clone that replaces normal cells.

Question 12

What are some of the abnormal behaviours of a leukaemic clone?

Answer 12

1. Growth that occurs without a dependence on growth factors.
2. Continued proliferation without maturation
3. Failure to undergo normal cell death (apoptosis)
4. Not enjoying James Pease’s mini-history lessons in the GOLs.

Question 13

How could we generally describe the causes of Leukaemias?

Answer 13

They are usually unknown.

Question 14

What is one potential reason for acute myeloid leukaemia (AML)?

Answer 14

As it usually develops later in life, it is believed to be as a result of spontaneous mutations. This could be due to the inevitable consequence of our ability to evolve, and so mutate, or in part due to exposure to irradiation of mutagenic drugs.

Question 15

When do most Acute Lymphoblastic Leukaemia mutations occur?

Answer 15

Most start in utero, during foetal development.

This could be caused by exposure to mutagenic drugs, irradiation, chemicals, pathogens…

Question 16

What is one potential cause of chronic lymphoid/lymphocytic leukaemia?

Answer 16

Some families have a genetic predisposition to it.

Question 17

What type of leukaemia is rarely due to irradiation or mutagenic drugs?

Answer 17

Chronic myeloid leukaemia.

Question 18

What are acute leukaemia often the result of?

What does this cause?

Answer 18

Mutations in genes that encode for transcription factors, causing a profound abnormality in the cell’s ability to mature.
Despite this, the cells continue to proliferate. This causes an accumulation of primitive cells known as blast cells, either myeloblasts or lyphoblasts.

Question 19

What are chronic leukaemia often the result of?

What does this cause and how does this differ between myeloid and lymphoid cells?

Answer 19

A mutation in a gene that involves the activation of signalling pathways within a cell, leading to cells being able to proliferate without needing growth factors. The cell survival is prolonged and there is a steady expansion of clone cells but maturation still occurs.
For myeloid cells, the mature end cells are still able to function, causing less impairment.
For lymphoid cells, although the mechanisms are less well understood, they lead to a steady expansion of clone cells, but are functionally useless, causing eventually tissue function impairment.

Question 20

The signs and symptoms of leukaemia are caused by both the direct and indirect effects of the proliferation of leukaemic cells.

What symptoms do they cause? For each one, state whether it is a direct result or indirect result.

Answer 20

Fatigue, lethargy and pallor are caused by anaemia, which is an indirect effect of leukaemic cell proliferation as normal bone marrow cells get replaced.

Fever and infections are caused by neutropenia, which is also an indirect result of bone marrow replacement.

Bruising and petechia (clusters of red/purple spots) are caused by thrombocytopenia, yet another indirect consequence as a result of bone marrow cells being replaced.

Bone pain, abdominal enlargement as a result of hepatomegaly and splenomegaly and swollen lymph nodes are some direct effects of leukaemic cell proliferation.

Question 21

How do we analyse the blood of a patient who we think has leukaemia?

Answer 21

We take a full blood count and look at a blood film.
We also need to characterise the profile of the cell surface markers expressed to distinguish between different cells (e.g. T and B lymphoid cells) using flow cytometry.
We can also look at the bone marrow/ blood of a patient to look for markers such as the Philadelphia chromosome.

Question 22

What does cytogenic and molecular genetic analysis allow?

Answer 22

It allows us to gather information on the prognosis as well as advance our knowledge of leukaemia.