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L14 Pathogenesis of Myeloid Neoplasia
Leukaemic Stem cells
 Acute myeloid leukaemia accumulation of primitive stem cells in bone marrow
o Transcription factors in myeloid development mutated in AML
o E
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GATA
 Differentiation in stroma of bone marrow
o If niche isn’t right may develop a leukaemia
 Absence of certain transcription factors blood cell
differentiation is blocked  can become a leukaemia
cell
 Myeloid leukemic stem cells derived from stem cells or
multipotent progenitors
 Myeloid dysplasia is a pre-cancer cells
o MDS – heterogeneous clonal disorder of blood
cell production – acquisition of a number of
heterogenous changes (genetic and epigenetic)
that sequentially haemopoietic cell fate
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g
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If you have one the other is more likely to be
present of develop
 Clonal selection in disease progression from myelodysplastic syndrome to acute myeloid leukaemia
o Clonal evolution – if you are treated more than once the biology of the cells change those that
were not killed survive = if not cured 1st time will be harder to cure after each treatment
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AML do well with treatment
Those that may form RBCs or platelets are less likely to have FLT3 mutation
Nucleoplasmic gene (NPM1) is a nuclear shuttling protein
o Patients with AML with NPM1 mutations without FLT3 and a normal karyotype have a good
prognosis
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g

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