The AML phenotype requires 2 or more co-operating mutations within one hematopoietic Stem cell 1. Loss of function mutations block maturation 2. Gain of function mutations cause constitutive activation of signalling pathways enhancing proliferation and/or survival. These 2 fundamental requirements may be supplemented by: a) mutations/deletions of tumour suppressor genes b) overexpression of anti-apoptosis genes such as BCL-2 c) epigenetic changes involving chromatin remodeling d) interactions with the microenvironment i. cytokines ii. growth factors e) angiogenesis f) MDR phenotypes The phenotype, treatment and outcome will depend on the combination of factors in a given patient.
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