Alternative routes to IRAK1 activation include upregulation of upstream positive regulators, such as seen with PIN1 (see above) as well as S100A-7/9 proteins in breast cancers with 1q21.3 amplification (53); mutational inactivation or downregulation of negative regulators such as miR-146a, as seen in del(5q) acute myeloid leukemia (54); and likely additional mechanisms [reviewed in (4, 19)]. The gene discussed is IRAK1; the disease is breast carcinoma.