Key Points• EPHB4 promotes leukemia survival via AKT activation.• EPHB4 can be therapeutically targeted in AML with monoclonal antibodies.EPHB4, an ephrin type B receptor, is implicated in the growth of several epithelial tumors and is a promising target in cancer therapy; however, little is known about its role in hematologic malignancies. In this article, we show that EPHB4 is highly expressed in ;30% of acute myeloid leukemia (AML) samples. In an unbiased RNA interference screen of primary leukemia samples, we found that EPHB4 drives survival in a subset of AML cases.Knockdown of EPHB4 inhibits phosphatidylinositol 3-kinase/AKT signaling, and this is accompanied by a reduction in cell viability, which can be rescued by a constitutively active form of AKT. Finally, targeting EPHB4 with a highly specific monoclonal antibody (MAb131) is effective against AML in vitro and in vivo. EPHB4 is therefore a potential target in AML with high EPHB4 expression.

Seismic moment and rupture length can be combined to infer stress drop, a key parameter for assessing earthquakes. In natural earthquakes, stress drops are largely depth‐independent, which is surprising given the expected dependence of frictional stress on normal stresses and hence overburden. We have developed a transparent experimental fault that allows direct observation of thousands of slip events, with ruptures that are fully contained within the fault. Surprisingly, the observed stress drops are largely independent of both the magnitude of normal stress and its heterogeneity, capturing the independence seen in nature. However, we observe larger, normal stress‐dependent stress drops when the fault area is reduced, which allows slip events to frequently reach the edge of the interface. We conclude that confined ruptures have normal stress independent stress drops, and thus the depth‐independent stress drops of tectonic earthquakes may be a consequence of their confined nature.

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