Ibrutinib (PCI-32765) is an irreversible BTK (Bruton’s tyrosine kinase) kinase inhibitor that has been extensively used as a tool compound to validate the role of BTK kinase in B cell related malignances. 1, 2 Ibrutinib has been shown in preclinical studies to inhibit the proliferation of diffuse large B-cell lymphoma cells, mantle cell lymphoma cells, chronic lymphocytic leukemia cells and multiple myeloma cells by blocking BTK kinase activity; ibrutinib was recently approved for the clinical application on mantle cell lymphoma and chronic lymphocytic leukemia cells. 3–7 Ibrutinib has also exhibited anti-inflammatory effects in preclinical models. 8, 9 Recently, it has been reported that ibrutinib is also effective against epidermal growth factor receptor mutantpositive non-small cell lung cancers through inhibition of epidermal growth factor receptor kinase activities. 10 In addition, there is evidence showing that BTK is also an important target for Acute Myeloid Leukemia (AML). 11 Despite the evidence that BTK knockdown impaired AML cancer cell growth, which suggested that BTK was important for AML cell proliferation, BTK kinase inhibition through use of a small molecule inhibitor like ibrutinib led only to moderate inhibition of proliferation of U937 cells with no apparent activity against other AML cell lines such as HL-60, TF-1 and THP-1. 11 To further investigate the potency and activity of ibrutinib against AML, we screened a panel of AML cell lines spanning M0–M7 disease stages. Interestingly, we found that only FLT3-internal tandem duplication (ITD) mutant AML cell lines (MOLM13, MOLM14 and MV4-11) were sensitive to ibrutinib (Figure 1a and Supplementary Table 1). This is similar to what has been observed with the highly