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10.1158/0008-5472.CAN-15-2092 http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-15-2092 C4794354!4794354!26801976     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 302.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 302.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 302.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cancer+Res 2016 ; 76 (6): 1641-52 Nephropedia Template TP {{tp|p=26801976|t=2016. Aberrant Notch signaling in the bone marrow microenvironment of acute lymphoid leukemia suppresses osteoblast-mediated support of hematopoietic niche function |pdf=|usr=}}{{26801976}} gab.com Text Aberrant Notch signaling in the bone marrow microenvironment of acute lymphoid leukemia suppresses osteoblast-mediated support of hematopoietic niche function JO: Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=26801976 #FOAvip More than half of T-ALL patients harbor gain-of-function mutations in the intracellular domain of Notch1. Diffuse infiltration of the bone marrow commonly occurs in T-ALL and relapsed B-ALL patients, and is associated with worse prognosis. However, the mechanism of leukemia outgrowth in the marrow and the resulting biological impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular and molecular abnormalities in leukemia marrow stroma responsible for the suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts. We found that actively proliferating leukemia cells inhibited normal hematopoietic stem and progenitor cell (HSPC) proliferation and homing to the peri-vascular region. In addition, leukemia development was accompanied by the suppression of the endosteum-lining osteoblast population. We further demonstrate that aberrant Notch activation in the stroma plays an important role in negatively regulating the expression of CXLC12 on osteoblasts and their differentiation. Notch blockade reversed attenuated HSPC cycling, leukemia-associated abnormal blood lineage distribution and thrombocytopenia as well as recovered osteoblast and HSPC abundance and improved the hematopoietic-supportive functions of osteoblasts. Finally, we confirmed that reduced osteoblast frequency and enhanced Notch signaling were also features of the marrow stroma of human ALL tissues. Collectively, our findings suggest that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. Twit Text FOAVip Aberrant Notch signaling in the bone marrow microenvironment of acute lymphoid leukemia suppresses osteoblast-mediated support of hematopoietic niche function ????Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=26801976 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26801976 #FOAvip English Wikipedia <ref>{{Cite pmid|26801976}}</ref> Aberrant Notch signaling in the bone marrow microenvironment of acute lymphoid leukemia suppresses osteoblast-mediated support of hematopoietic niche function #MMPMID26801976 Wang W; Zimmerman G; Huang X; Yu S; Myers J; Wang Y; Moreton S; Nthale J; Awadallah A; Beck R; Xin W; Wald D; Huang AY; Zhou L Cancer Res 2016[Mar]; 76 (6): 1641-52 PMID26801976show ga More than half of T-ALL patients harbor gain-of-function mutations in the intracellular domain of Notch1. Diffuse infiltration of the bone marrow commonly occurs in T-ALL and relapsed B-ALL patients, and is associated with worse prognosis. However, the mechanism of leukemia outgrowth in the marrow and the resulting biological impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular and molecular abnormalities in leukemia marrow stroma responsible for the suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts. We found that actively proliferating leukemia cells inhibited normal hematopoietic stem and progenitor cell (HSPC) proliferation and homing to the peri-vascular region. In addition, leukemia development was accompanied by the suppression of the endosteum-lining osteoblast population. We further demonstrate that aberrant Notch activation in the stroma plays an important role in negatively regulating the expression of CXLC12 on osteoblasts and their differentiation. Notch blockade reversed attenuated HSPC cycling, leukemia-associated abnormal blood lineage distribution and thrombocytopenia as well as recovered osteoblast and HSPC abundance and improved the hematopoietic-supportive functions of osteoblasts. Finally, we confirmed that reduced osteoblast frequency and enhanced Notch signaling were also features of the marrow stroma of human ALL tissues. Collectively, our findings suggest that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. äAberrant Notch signaling in the bone marrow microenvironment of acute (epmc).pdf DeepDyve Pubget Overpricing