Combinations of ATO with other agents

Combining ATO with the antiangiogenic agent thalidomide, Raza et al. has recently shown that several MDS patients harboring an inv(3)(q21q26.2) abnormality achieved trilineage responses.36 This suggested that perhaps a gene(s) on chromosome 3 may be interacting with ATO to inhibit clonal proliferation. The human EVI-1 gene, located at chromosome 3q25-q28, has been shown to inhibit transcription of GATA-1

target genes and impair responsiveness of erythroid precursors to erythropoietin.36 This suggested that perhaps EVI-1 deregulation has a role in the pathogenesis of MDS and/or response to this therapeutic regime. EVI-1 was found to be abnormally expressed in five patients, with three out of five patients responding especially well to therapy.37 Accordingly, EVI-1 expression may be a useful preselection criterion for therapy with ATO +/- thalidomide.)

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