leukaemia Flashcards
what are leukaemias?
- heterogenous group of malignant blood disorders
- type of cancers caused by unregulated proliferation of a clone of immature blood cells derived from mutant haemoatopoietic stem cells
- arise as a result of multiple acquired genetic and epigentic events
percentage of leukaemias of total cancer cases is
3%
___ % of leukaemias in UK are male
60%
leukaemia locations
- bone marrow
- lymph system, including spleen
two types of bone marrow
red bone marrow
* red + white cells are made
* found in mature breast bone, skull, vertebrae, pelvis, ribs
yellow bone marrow
* made mostly of fat cells
* found in middle section of long bones
leukaemia aetiology ( causes )
- chromosomal translocation
- chromosomal deletion ( e.g. in AML a gene is lost )
- chromosomal addition ( usually a duplication )
- submicroscopic mutations ( change in base sequence of oncogenes )
- epigenic changes where gene code is ok, but function affected ( by methylation )
examples of some epigenetic factors
- environmental chemicals
- drugs/pharmaceuticals
- aging
- diet
pathophysiology of leukaemia
- normal bone marrow replaced by immature + undifferentiated leukocytes, stem cells and blast cells
- abnormal immature leukocytes ciruclate in blood + infiltrate liver, spleen and lymph nodes
- myeloid proliferation —-> no space for lymphoid cells to develop + WBC numbers fall
- lymphoid prolifertaion —-> reduced red cells + platelets
predisposing factors of leukaemia
- smoking
- previous chemotherapy
- occupational chemical exposure
- down’s syndrome
- myeloproliferative disorders
classifying leukaemias
acute myeloid leukaemia - list clinical mainfestations
- marrow failure
- tissue infiltration
- leukostasis and DIC
- sternal tenderness
acute myeloid leukaemia - what does marrow failure cause?
neutropenia
* more infections; sepsis
anaemia
* fatigue; pallor
thrombocytopenia
* bleeding; brusing
acute myeloid leukaemia - what does tissue infiltration cause?
- organomegaly - liver, spleen, lymph nodes
- gum hypertrophy
- bone pain
acute myeloid leukaemia - what does leukostasis cause?
accumulation of cells in microcirculation impairs perfusion causing
* hypoxaemia
* stroke
* fever and sweats
* headacches
disseminated intravascular coagulation ( DIC )
acute myeloid leukaemia diagnosis
- WCC ofetn high, could be normal/low
- anaemia + thrombocytopenia common
- blood film - many blast cells or dysplactic changes to cellls
- diagnosis confirmed by bone marrow aspirate
- difficult to distinguish from ALL so cell staining used
- results with sudan black — > +ve AML, -ve ALL
acute lymphoblastic leukaemia incidence
- 75% cases under 6yr
- twice likely in white than black people
- being pregnant increases risk
- fatal within months if untreated ( 3 months )
acute lymphoblastic leukaemia - symptoms
- weakness
- weight loss
- bruising easily
- bleeding from gums and nose
- fever
- swollen lymph glands
acute lymphoblastic leukaemia - examination
- Palpable liver (64%)
- Palpable spleen (61%)
- Pale appearance (54%)
- Fever (52%)
- Bruising (52%)
- arm/leg pain
- enlarged lymph node
- testicular enlargement
acute lymphoblastic leukaemia - diagnosis
- WCC may be raised, normal, low
- anaemia + thrombocytopenia common
- bone marrow aspirate essential
- stains positive for AML, negative for ALL
- immunophenotyping essential for chromosomal abnormalities
what is chronic myeloid leukaemia?
myeloproliferative disorder resulting from an acquired genetic change to a pluripotent stem cell
chronic myeloid leukaemia phases
chronic myeloid leukaemia - pathogenesis
more than 90% of cases result from the Philadelphia chromosome
what is the only treatment for CML?
stem cell transplantation
what is chronic lymphocytic leukaemia?
- proliferation of B-lymphocytes
- most common form of leukaemia
chronic lymphocytic leukaemia - cause
thought to be caused by benzene exposure or high doses of ionising radiation
chronic lymphocytic leukaemia - symptoms
- often no symptoms
- some have fatigue, weakness, fever, weight loss, joint pain
chronic lymphocytic leukaemia - examination
- enlarged spleen, liver or lymph nodes
- pruritic vesicular lesions
chronic lymphocytic leukaemia - examination
- anaemia, thrombocytopenia
- elevated WCC
- increased blood viscosity and clotting
chronic lymphocytic leukaemia prognosis