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Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.

Cancer cell | Sep 11, 2017

The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies. Moreover, induction chemotherapy failing to restore normal vasculature was associated with a poor prognosis. Inhibition of NO production reduced vascular permeability, preserved normal hematopoietic stem cell function, and improved treatment response in PDX.

Pubmed ID: 28870739 RIS Download

Mesh terms: Animals | Antineoplastic Agents | Bone Marrow | Capillary Permeability | Cellular Microenvironment | Disease Progression | Gene Expression Profiling | Gene Expression Regulation, Leukemic | Hematopoietic Stem Cells | Humans | Leukemia, Myeloid, Acute | Mice | Neoplasm Transplantation | Nitric Oxide | Treatment Outcome

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ATCC

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene

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Interactive Vision In The Life SciencesCombining speed, precision and ease-of-use, Imaris provides an impressive range of capabilities for working with three-dimensional images. Move easily between simple and advanced 3D views. Use flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.BitPlane, Inc. also releases the following companion products:- ImarisXT is a multi-functional two-way interface from Imaris to both classic programming languages and to Matlab.- Imaris MeasurementPro and Imaris Track provide the ability to segment and follow the movement of independent objects in a 3D image over time. Objects can either be Surface Objects or Spots, created automatically or manually.- ImarisColoc enables users to easily isolate, visualize, and quantify regional overlap in 3D and 4D images and automates the process of selecting colocalized image areas.

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Jackson Laboratory

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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