Stegmaier K et al. (2005) Gefitinib (Iressa) induces myeloid differentiation of acute myeloid leukemia. Blood 106: 2841–2848

Investigators have identified an FDA-approved drug that increases the degree of myeloid maturation in patients with mutations in differentiation-promoting transcription factors. They advocate gefitinib (Iressa®, AstraZeneca UK Limited, London, UK) as a promising alternative to cytotoxic agents for treating acute myeloid leukemia (AML).

Stegmaier et al. found neutrophilic and myeloid differentiation in AML cell lines (HL-60 and Kasumi-1) that had been treated with 10 μM gefitinib for 4 days. After 6 and 24 hours of 10μM gefitinib treatment, the two cell lines demonstrated significant genome-wide gene expression of neutrophil maturation. This was also evident in the AML cell blasts obtained from eight patients. Consistent with the excellent clinical safety profile of gefitinib, the researchers found that cell viability was reduced in AML blasts but not in normal donor blood cells. Previous assumptions that EGFR or ERBB2 inhibition is involved in the mechanism behind differentiation were proved false as EGFR and ERBB2 transcripts were undetectable in HL-60 and Kasumi-1 cell lines.

Gefitinib binds to a large number of different kinases and the mechanism might involve inhibition of one or a combination of these. Further study into the drug's functioning, and immediate commencement of clinical trials are essential if we are to make use of this exciting development.