CHRONIC MYELOID LEUKAEMIA Flashcards
what is chronic myeloid leukaemia
cancer of white blood cells characterised by uncontrolled growth of the myeloid cells in the bone marrow
which chromosomal abnormality causes CML
philadelphia chromosome
translocation between 9 and 22 (BCR-ABL)
how does the BCR-ABL mutation result in malignant growth
the gene is able to add phosphates to tyrosine residues (a tyrosine kinase) and this allows BCR-ABL to activate a cascade of proteins which control the cell cycle, speeding up cell division
it also inhibits DNA repair
how do patients generally present
asymptomatically, with an elevated WCC on routine blood test
symptoms of CML include
upper abdominal pain poor appetite low grade fever/night sweats gout increased susceptibility to infection SOB/fatigue easy brushing/petechiae/bleeding neurological deficits/visual disturbance
why does CML predispose to gout
increased cell turnover –> excess purines –> broken down to uric acid
what are the three phases of CML
chronic phase
accelerated phase
blast crisis
what are features of the chronic phase
asymptomatic/mild symptoms
variable duration
what are the criteria of the accelerated phase
10-19% myeloblasts in blood or bone marrow
> 20% basophils in the blood or bone marrow
platelet count <100,00, unrelated to therapy
platelet count >1,000,000, unresponsive to therapy
cryogenic evolution with new abnormalities
increasing splenomegaly or WCC, unresponsive to therapy
what is blast crisis
final phase of CML, in which the disease behaves like an acute leukaemia, with rapid progression and short survival
how is blast crisis diagnosed
> 20% myeloblasts or lymphoblasts in blood or bone marrow
large clusters of blasts in the bone marrow on biopsy
development of chroma (solid focus of leukaemia outside bone marrow)
what does FBC show in CML
leukocytosis
increased EO and BA
differential WCC shows granulocytes at all stages of development
anaemia (normo/normo)
what does biochemistry show in CML
lactacte dehydrogenase is often raised
rate may be raised
U&Es are usually normal at presentations
what does peripheral blood film show in CML
all stages of granulocyte maturation
appearances similar to that of a bone marrow aspirate
why is bone marrow aspirate necessary
to stage disease (% of blasts determines chronic vs accelerated vs blast crisis)
allows cryogenic sampling (Philadelphia chromosome)
