Acute Myeloid Leukemia Pathway

Two major types of genetic events are crucial for the molecular pathogenesis of acute myeloid leukemias (AML): activating mutations of signal transduction intermediates and alterations in myeloid transcription factors governing hematopoietic differentiation. Both aberrant and constitutive activation of signal transduction molecules are found in about 50% of primary AML bone marrow samples, and seem to contribute to the increased proliferation and apoptosis resistance. The most common of these activating events were observed in the RTK Flt3, in N-Ras and K-Ras, in Kit, and sporadically in other RTKs. Specific haematopoietic transcription factors are crucial for differentiation to particular lineages during normal differentiation, but are frequently disrupted in AML. Some mechanisms of disruption involve the effect of fusion proteins that are generated by chromosomal translocations on haematopoietic transcription factors. In other cases, the transcription factors themselves are mutated. (NCI Thesaurus/KEGG)

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