L24 - Introduction to Leukaemia Flashcards
Define Leukaemia?
malignant disorders of haematopoietic stem cells characteristically associated with an increase of white blood cells in bone marrow or/and peripheral blood.
What are Haematopoietic stem cells?
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
What are undifferentiated progenitor cells?
No difference between them morphologically because they do not show characteristics of mature cell. They are Multipotent.
What are committed progenitor cells?
already committed as to what they will become when they generate mature cells. They are unipotent
How does Leukaemia arise?
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.
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Describe the symptoms of Leukaemia?
- abnormal bruising
- repeating abnormal infection
- sometimes anaemia
What 3 tests can be used to diagnose Leukaemia?
- 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)
What are some genetic risk factors for Leukaemia?
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
What are some environmental risk factors for Leukaemia?
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
What are some lifestyle related factors linked with Leukaemia?
smoking
drinking
excessive exposure to the sun
overweight
What are some controversial risk factors linked with Leukaemia?
- exposure to electromagnetic fields
- infections in early life
- mother’s age when child is born
- nuclear power stations
- parent smoking history
What are the 4 types of Leukaemia?
Acute Lymphoid Leukaemia
Acute Myeloid Leukaemia
Chronic Lymphoid Leukaemia
Chronic Myeloid Leukaemia
What is meant by acute Leukaemia?
rapid onset an short but severe course
- undiffeentiated leukaemeia
- characterised by uncontrolled accumulation of immature white blood cells (blasts)
What are the characteristics of a patient with acute leukaemia?
- mainly children
- the onset is sudden
- lasts weeks to months
- white blood cell count is variable
What is meant by chronic Leukemia?
persisting over a long time
- differentiated leukaemia
- characterised by accumulation of mature white blood cells (cytes)
What are the characteristics of a patient with chronic Leukaemia
- middle age and elderly
- onset is insidious
- lasts years
- white blood cell count is high
What are the symptoms of Acute Leukaemia due to bone marrow supression?
- Thrombocytopenia: Purpura (bruising), epistaxis (nosebleed) and bleeding from gums
- Neutropenia: recurrent infections and fever
- Anaemia: lassitude, weakness, tiredness and shortness of breath
Describe Acute Lymphoid/Lymphoblastic Leukaemia including its treatment?
commonest cancer of childhood
B-cell and T-cell leukaemia
treatment is chemotherapy
Describe Acute Myeloid/Myeloblastic Leukaemia including its treatment?
classification is M0-M7
treatement is chemotherapy, monoclonal antibodies (immunotherapy), and allogenic bone marrow transplant
Describe Chronic Lymphoid/Lymphocytic Leukaemia including its treatment?
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
Describe Chronic Myeloid/Granulocytic Leukaemia including its treatment?
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
Decsribe how the BCR-ABL oncogene occurs and what type of Leukaemia it is associated with?
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.
What does the BCR and ABL genes do separately and what happens when they join together?
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
What occurs as a result of the BCR-ABL Oncogene?
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
Describe Imatinib as targeted therapy for pateints with chronic myeloid Leukaemia?
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
