Introduction to Leukaemia Flashcards
Define Leukemia
This is a group of malignant disorders of hematopoietic stem cells characteristically associated with increase number of white cells in bone marrow /peripheral blood
What cells does Leukemia affect ?
Lymphocytes Neutrophils Lymphocyte Monocyte Platelets
What are hematopoietic stem cells (HSCs)
These stem cells are multipotent meaning they can give rise to cells of every blood lineage
Self maintaining -Stem cell can divide to produce more stem cells
When they divide they can be asymmetric or symmetric.
Following asymmetric division it forms more differentiated cells with less potency capacity
What are progenitor cells ?What are formed from haematopoietic stem cells?
Haematopoietic stem cells can produce :
Common myeloid progenitor and Common lymphoid progenitor
- Can divide to produce many mature cells
- Cannot divide indefinitely
- Eventually differentiate and mature
What types of progenitor cells are there ?
- Undifferentiated (multipotent)
You cannot differentiate between myeloid /lymphoid because they do not show the characteristics of mature cells
2.Totipotent/unipotent progenitors
These are committed progenitor cells and have already committed to what they will become when they generate mature cells.
What type of disease is leukaemia ?
It is a clonal disease-
All the malignant cells derive from a single mutant stem cell
There is a genetic alteration in one of the stem cells or progenitors.
Can cause overexpression of certain transcription factors.
The cells can permanently divide and will be continuously active.
Outline what happens to give rise to a leukaemia stem cell
There is a mutation in a haematopoietic stem cell which leads to continuous self renewal and through clonal evolution , this gives rise to leukemic cells. They will permanently divide.
The oncogenic transcription factors will drive the progenitors/haematopoietic stem cells to a pre-leukemic stage through an arrest in differentiation and acquisition in cell renewal properties. The second mutation will then form leukaemia through self renewal and survival proliferation
Outline the incidence of leukaemia
Leukaemia is most common in people who are aged 75 and older . Peak rate (85-89) years old
Describe the presentation of leukaemia ?
Varies between types of leukaemia
Typically first presents with symptoms due to loss of normal blood cell production :
- Abnormal bruising-commonest (due to abnormal production of platelets )
- Repeating abnormal infection (absence of white blood cells )
-Sometimes anaemia
(reduced production of RBC)
What causes anaemia in Leukaemia ?
Reduced production of RBC
In the bone marrow , three lineages of cells are formed:
WBC, RBC and platelets
However in Leukaemia there will not be production of these cells.
Fatigue
Loss of Immune power
Fever
Dizziness
How can we diagnose Leukaemia ?
1.When a biopsy is extracted from bone marrow .
Taken from pelvic bone and results compared with PB
Peripheral blood blasts tests (PB)
To check for presence of blasts and cytopenia
>30% blasts are suspected of acute leukaemia
Lumbar puncture- To determine if the leukaemia has spread to the cerebral spinal fluid
What are the ways in which we can categorise Leukaemia ?
Cytomorphology Immunophenotyping Next generation sequencing Fluorescence in situ (FISH) Hybridisation Flow cytometry
What is the cause of Leukamia ?
Not usually hereditary
Usually somatic genetic alterations
Some rare genetic diseases may predispose to leukaemia :
Fanconi’s anaemia , Downs syndrome
What are the genetic risk factors of Leukaemia ?
Gene mutations involving oncogenes (activation ) or tumour suppressors (inactivation)
-Involving genes common to other malignancies (TP53-Li-Fraumeni syndrome, NF1-Neurofibromatosis) or specific to leukaemia
Chromosome aberrations:
- Translocations (BCR-ABL in CML) -95% of chronic myeloid leukaemia
- Numerical disorders (trisomy 21)
Inherited immune system problems:
- Ataxia telangiectasia
- Wiskott-Aldrich syndrome
What are some environmental risk factors ?
Radiation exposure :
- Acute radiation accidents
- Atomic bomb survivors
Exposure to chemicals and chemotherapy
- Cancer chemotherapy with alkylating agents
- Industrial exposure to benzene
Immune system suppression
-Organ transplant
What are some lifestyle related risk factors ?
Adult cancers : Smoking Drinking Excessive sun exposure Overweight
What are some possible childhood leukaemia causes ?
- Exposure to electromagnetic fields
- Nuclear power stations
- Infections during early life
- Parents smoking history
- Foetal exposure to hormones
- Mothers age when child is born
What is the classification of Leukaemia ?
There are four types:
- Acute Lymphoid/Lymphoblastic leukaemia
- Chronic Lymphocytic leukaemia
- Acute Myeloid/Myeloblastic leukaemia
- Chronic Myeloid/Granulocytic leukaemia
What does acute leukaemia mean?
Acute means a rapid onset and short but severe course
-Undifferentiated leukaemia
Characterised by uncontrolled clonal and accumulation of immature white blood cells (-blast )
Blast are immature cells e.g Myeloblast /Lymphoblast
Outline what chronic leukaemia is ?
This is a disease which persists over a long time
Chronic leukaemia :
Differentiated leukaemia
Characterised by uncontrolled clonal and accumulation of mature white blood cells ( -cyte )
Cytes are cells which have differentiated
What are the main differences between acute and chronic ?
Age :
Acute -Children / Chronic-Middle aged
Onset :
Acute -Sudden / chronic -Insidious
Duration:
Acute -Weeks/month / chronic -years
WBC counts :
Acute -variable / chronic -high
How is acute leukaemia characterised ?
It is characterised by a large number of lymphoblast’s aor myeloid blasts in bone marrow and blood-undifferentiated leukaemia
High number of blasts
What causes an increase in blast cells in Acute Leukaemia ?
Normally the process is :
Cell proliferation - Blast cell pool-Mature cells -Cell death (Apoptosis /Necrosis )
In acute leukaemia
Cell proliferation -Blast cell pool - (Maturation arrest )
Some cells will die before maturing
What are the typical symptoms of acute leukaemia ?
The typical symptoms are due to bone marrow suppression :
Thrombocytopenia :purpura (bruising), epistaxia (nose bleed ), bleeding from gums
Neutropenia : Recurrent infections , fever
Anaemia :Lassitude , weakness , tiredness , shortness of breath
Might take a bone marrow biopsy to confirm
