L24 - Introduction to Leukaemia Flashcards

1
Q

Define Leukaemia?

A

malignant disorders of haematopoietic stem cells characteristically associated with an increase of white blood cells in bone marrow or/and peripheral blood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are Haematopoietic stem cells?

A

they are multipotent stem cells that can gove rise to cells of every blood lineage. It is self-maintaining and can divide to produce more stem cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are undifferentiated progenitor cells?

A

No difference between them morphologically because they do not show characteristics of mature cell. They are Multipotent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are committed progenitor cells?

A

already committed as to what they will become when they generate mature cells. They are unipotent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does Leukaemia arise?

A

A primary mutation is required in only one of the haematopoietic stem cells .
And then a second mutation is needed in either the mutlipotent progenitors or the common myeloid progenitors or common lymphoid progenitors.
I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the symptoms of Leukaemia?

A
  • abnormal bruising
  • repeating abnormal infection
  • sometimes anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What 3 tests can be used to diagnose Leukaemia?

A
  • peripheral blood blasts test (checks presence of blasts and cytopenia. Higher than 30% blasts are suspected of acute leukaemia)
  • bone marrow test/ biopsy (taken from pelvic bone and results are compared with peripheral blood blasts test)
  • Lumbar puncture (to determine if the leukaemia has spread to cerebral spinal fluid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are some genetic risk factors for Leukaemia?

A

It is not usually hereditary
- some rare genetic diseases may lead to leukaemia: like Faconi’s anaemia and Down’s syndrome

  • gene mutations that invlove oncogenes activation or tumour supressor genes inactivation that are inherited could cause Leukaemia
  • Inherited immune system problems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are some environmental risk factors for Leukaemia?

A

RADIATION EXPOSURE:

  • acute radiation accidents
  • atomic bomb survivors

EXPOSURE O CHEMICALS AND CHEMOTHERAPY:

  • cancer chemotherapy with alkylating agents
  • industrial exposure to benzene

IMMUNE SYSTEM SUPPRESSION:
- after organ transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some lifestyle related factors linked with Leukaemia?

A

smoking
drinking
excessive exposure to the sun
overweight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some controversial risk factors linked with Leukaemia?

A
  • exposure to electromagnetic fields
  • infections in early life
  • mother’s age when child is born
  • nuclear power stations
  • parent smoking history
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the 4 types of Leukaemia?

A

Acute Lymphoid Leukaemia
Acute Myeloid Leukaemia
Chronic Lymphoid Leukaemia
Chronic Myeloid Leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is meant by acute Leukaemia?

A

rapid onset an short but severe course

  • undiffeentiated leukaemeia
  • characterised by uncontrolled accumulation of immature white blood cells (blasts)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the characteristics of a patient with acute leukaemia?

A
  • mainly children
  • the onset is sudden
  • lasts weeks to months
  • white blood cell count is variable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is meant by chronic Leukemia?

A

persisting over a long time

  • differentiated leukaemia
  • characterised by accumulation of mature white blood cells (cytes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the characteristics of a patient with chronic Leukaemia

A
  • middle age and elderly
  • onset is insidious
  • lasts years
  • white blood cell count is high
17
Q

What are the symptoms of Acute Leukaemia due to bone marrow supression?

A
  • Thrombocytopenia: Purpura (bruising), epistaxis (nosebleed) and bleeding from gums
  • Neutropenia: recurrent infections and fever
  • Anaemia: lassitude, weakness, tiredness and shortness of breath
18
Q

Describe Acute Lymphoid/Lymphoblastic Leukaemia including its treatment?

A

commonest cancer of childhood
B-cell and T-cell leukaemia
treatment is chemotherapy

19
Q

Describe Acute Myeloid/Myeloblastic Leukaemia including its treatment?

A

classification is M0-M7

treatement is chemotherapy, monoclonal antibodies (immunotherapy), and allogenic bone marrow transplant

20
Q

Describe Chronic Lymphoid/Lymphocytic Leukaemia including its treatment?

A

Large numbers of mature lymphocytes in bone marrow and peripheral blood.

Recurrent infections due to neutropenia, and lymph node enlargement, hepatosplenomegaly

treatment is regular chemotherapy

21
Q

Describe Chronic Myeloid/Granulocytic Leukaemia including its treatment?

A

Large numbers of mature myeloid white blood cells in bone marrow and peripheral blood.

Often asymptomatic and discovered through routine blood tests

presence of philedalphia chromosome

treatment is targeted therapy: Imatinib

22
Q

Decsribe how the BCR-ABL oncogene occurs and what type of Leukaemia it is associated with?

A

Occurs in 95% cases of chronic Myeloid Leukaemia.

A balanced translocation between chromosome 9 and chromosome 22 occurs:

The ABL gene from chromosome 9 breaks off and a part of chromosome 22 including the BCR gene is left behind when some of it breaks off. The BCR gene from chromosome 22 and the ABL gene from chromosome 9 join together to form the new chromosome 22 (this is the philadelphia chromosome).

The remaining part of chromosome 22 joins with the remaining part of chromosome 9 to form the new chromsome 9.

23
Q

What does the BCR and ABL genes do separately and what happens when they join together?

A

The BCR gene encodes a protein that needs to be continously active.

The ABL gene encodes a protein tyrosine kinase whose activity is tightly regulated.

The BCR-ABL oncogene has contitutive (unregulated) protein tyrosine kinase activity

24
Q

What occurs as a result of the BCR-ABL Oncogene?

A

its causes unregulated tyrosine kinase activity and in the bone marrow it causes:

  • proliferation of progenitor cells in the absence of growth factors
  • decreased apoptosis
  • decreased adhesion to bone marrow stroma
25
Q

Describe Imatinib as targeted therapy for pateints with chronic myeloid Leukaemia?

A

Only used as treatment for the cases that have the BCR-ABL gene. Approved in 2002.

It is a small molecule inhibitor that targets ABL specifically. BCR-ABL molecule requires ATP to phosphorlyate the substrate, however Imatinib, binds to BCR-ABL fusion protein instead of ATP. This means that the BCR-ABL protein cannot phosphorylate its substrate and therefore annot activate it.

Some patients can become drug resistant