Introduction To Leukaemia Flashcards
Define leukemia
Malignant disorders of haematopoeitic stem cells associated with increased number of white blood cells in bone marrow and/or peripheral blood
What does luekocytes include?
Neutrophils, eosinophils, basophils, monocytes, lymphocytes
What type pf stem cells are haemotopoeitc stem cells?
Multipotent - can give rise to cells of all blood lineage (not myeloid or lymphoid progenitor yet)
How do stem cells produce new stem cells?
Asymmetrical division so new cells have less potency
How do progenitor cells dividie?
Divide to produce mature cells but not indefiinitely
Eventually must differentiate and mature (from asymmetrical division)
What are progenitor cells?
Unidiffereniated multipotent cells - cant tell morphology difference between diff progenitors but still give risk to diff types of cells
How does potency change through haematopoeisis?
Potency decreases
What type of disease is leukemia?
Cloncal disease - all malignant cells derived from single mutant stem cell
How many mutations are there causing leukemia?
1st mutation is oncogenic - on transcription factor causing constant self renewal - over proliferation - causes pre-leukemic state
2nd mutation needed for full leukemia
How does leukemia present? (cause of symptoms and what are the syptoms)
Symptoms vary but caused by Loss of normal blood cell production
Symptoms
- abnormal bruising
- repeating abnormal infection - due to loss of immune function with lower WBCs
- sometimes anaemia
How do you diagnostic tests are done for leukemia? !!!!
Peripheral blood tests (PB) to check for presence of balsts and cytopenua (reduced number of mature red blood cells)
Bone marrow test/biopsy (BM) - taken from pelvic bone and compared to PB
Lumbar puncture - determines is leukemia has spread to cerebral spinal fluid (CSF)
How do you look for molecular and pathophysiological charactersation of leukemia when diagnosiing ? (methods to find molecular marker)
Cytomorpholoy Immunophenotyping Next generation sequencing (NGS)!!! to find causal variant FISH Flow cytometry
What types of predisposing factors are there for leukemia?
genetic risk factors
Environmental risk factors
Lifestyle generated risk factors
What are the genetic risk factors for leukemia?
Some rare genetic disease may predispose
Leukemia itself IS NOT hereditary apart from chronic lymphocytic leukemia (CLL)
Leukemia most often due to somatic mutations later in life
What rare genetic disease might predipsose to leukemia?
Fanconi’s anaemia
Down’s syndrome
another slide on egentic risk factors … oncogenes, tumour supressor genes and chromosme aberrations
What are the environmental risk factors for leukemia?
Radiation exposure
Exposure to chemicals and chemotherapy
Immune system suppression
What lifestyle factors may be risk factors for leuekemia?
Smoking
Drinking
Excessive exposure to sun
Overweight
What are the 4 classifications of leukemia?
Acute lymphoid (lymphoblastic) leukemia (ALL) Acute myeloid (myeloblastic) leukemia (AML) Chronic lymphoid (lymphocytic) leukemia (CLL) Chronic myeloid (myelocytic) leukemia (CML)
What is acute leukemia characterised by?
Uncontrolled clonal and accumulation of IMMATURE white blood cells (-blasts)
Lymphoblasts and myeloid blasts in bone marrow and blood
What is an acute disease?
Rapid onset and short but severe course
What is a chronic disease?
Persisiting over long time
How does chronic leukemia characterise?
Uncontrolled cloncal and accumulation of MATURE white blood cells (-cytes)
What shows in the blood count for acute leukemia vs chronic leukemia?
Acute - high number of blasts and WBC count is variable
Chronic - high number of mature white blood cells so WBC count is high
Who presents more with acute and who more with chronic leukemia?
Acute - children
Chronic - middle age to elderly
How can we see which type of acute leukemia it is?
can’t
still immature so cant tell if myeloid and lymphoid lineage
Which type of acute leukemia is more common?
ALL
Which leukemia is referred to undiffereniatied leukemia?
acute leukemia
What is the mechanism of acute leukemia?
Normallly blasts cells maure into mature cells then go through cell death at end of cell life
In leukemia, cell death doesnt happen inturn causing large blast cell pool (too many mature cells so blasts accumulate unable to differentiate into mature cells)
What are the typical symptoms of acute leukemia? and what is it caused by?
caused by bone marrow suppression
- thrombocytopenia - purpura (bruising), epistaxis (nose bleeds) and bleeding from gums
- Neutropenia - recurrent infection and fever
- Anaemia - weakness, tiredness and shortness of breath
What is the classification of acute lymphoblastic leukemia?
B cell and T cell leukemia
What is the treatment for acute lymphoblastic leukemia?
Chemotherapy
How is acute myeloblastic leukemia classified?
FAB system into M0-M7
What is the treatment for acute myeloblastic leukemia?
Chemotherpay, monoclonal antibodies in immunotherapy and allongeneic bone marrow transplant
What is differentiated leukemia?
Chronic leukemia because characterised with increased number of differentiated / mature cells
What are the symptoms of chronic lymphocytic leukemia?
Recurrent infections due to nuetropenia, suppression of normal lymphocyte function, anaemia, thrombocytopenia, lymph node enlargement and hepatosplenomegaly
What is the treatment for chronic leukemia?
Regular chemotherpay to reduce cell numbers
What are the symptoms for chronic myeloid/granulocytic leukemia?
Often asymptomatic, discovered through routine blood tests
How do you diagnose with chronic granulocytic.myeloid leukemia? !!
High white cell counts (nuetrophila) in blood and bone marrow
Presence of phildelphia chromosome
What si the treatment for chronic meyloid/granulocytic leukemia?!!!!!
Targted therapy - imatinib
In which leukemia type is detectale philadeliphia chromosome found?
CML
What is the philadeliphia chromosome formed by?
Chromosomal translocation between chromosome 9 and 22 joining the ABL on 9 with BCR on 22
