SUMMARY The role of the microenvironment in T cell acute lymphoblastic leukemia (T-ALL), or any acute leukemia, is poorly understood. Here we demonstrate that T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Cxcl12 deletion from vascular endothelial, but not perivascular, cells impeded tumor growth, suggesting a vascular niche for T-ALL. Moreover, genetic targeting of CXCR4 in murine T-ALL after disease onset led to rapid, sustained disease remission, and CXCR4 antagonism suppressed human T-ALL in primary xenografts. Loss of CXCR4 targeted key T-ALL regulators, including the MYC pathway, and decreased leukemia initiating cell activity in vivo. Our data identify a T-ALL niche, and suggest targeting CXCL12/CXCR4 signaling as a powerful therapeutic approach for T-ALL.

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Abstract-In this paper, we develop an analytical framework for evaluating multipath routing in mobile ad hoc networks. The instability of the topology (e.g., failure of links) in this type of network due to nodal mobility and changes in wireless propagation conditions makes transmission of time-sensitive information a challenging problem. To combat the inherent unreliability of these networks, we propose a routing scheme that uses multiple paths simultaneously by splitting the information between a multitude of paths, so as to increase the probability that the essential portion of the information is received at the destination without incurring excessive delay.Our scheme works by adding an overhead to each packet, which is calculated as a linear function of the original packet bits. The resulting packet (information and overhead) is fragmented into smaller blocks and distributed over the available paths. The probability of reconstructing the original information at the destination is derived in an analytical form and its behavior is studied for some special cases. It is shown that, under certain constraints, the packet dropping probability decreases as the number of used paths is increased.Index Terms-Ad hoc networks, ad hoc routing, alternative path routing, diversity coding, multipath routing, network fault tolerance, quality of service.