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1 January 2021
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Leukemia stem cell (LSC) plasticity in acute myeloid leukemia (AML) presents a major therapeutic challenge. In this issue, Stephanie Xie, John Dick, and colleagues characterize sphingosine-1-phosphate receptor 3 (S1PR3) as a plausible target in AML. Through extensive gene profiling in large AML patient datasets, the authors identify two AML subsets with different sphingolipid gene signature, responsiveness to the S1P prodrug fingolimod, and responsiveness to chemotherapy. S1PR3 expression on human HSC and LSC is induced by inflammatory cytokines and drives their myeloid differentiation in synergy with NF-κB signaling. Genetic and pharmacologic interrogation demonstrates how S1PR3 activation can drive AML cells into a differentiated state. This study offers detailed mechanistic insights into interconnections between metabolic, inflammatory, and myeloid differentiation circuits in HSC and LSC, and identifies two AML patient subgroups with distinct chemosensitivity. For details, please see the article on page 32 and the accompanying commentary by Toshio Suda and colleagues on page 3. - PDF Icon PDF LinkTable of Contents
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ISSN 2643-3230
EISSN 2643-3249
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Research Articles
Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation
Stephanie Z. Xie; Kerstin B. Kaufmann; Weijia Wang; Michelle Chan-Seng-Yue; Olga I. Gan; Elisa Laurenti; Laura Garcia-Prat; Shin-ichiro Takayanagi; Stanley W.K. Ng; ChangJiang Xu; Andy G.X. Zeng; Liqing Jin; Jessica McLeod; Elvin Wagenblast; Amanda Mitchell; James A. Kennedy; Qiang Liu; Héléna Boutzen; Melissa Kleinau; Joseph Jargstorf; Gareth Holmes; Yang Zhang; Veronique Voisin; Gary D. Bader; Jean C.Y. Wang; Yusuf A. Hannun; Chiara Luberto; Timm Schroeder; Mark D. Minden; John E. Dick
Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Helene Kretzmer; Anat Biran; Noelia Purroy; Camilla K. Lemvigh; Kendell Clement; Michaela Gruber; Hongcang Gu; Laura Rassenti; Arman W. Mohammad; Connie Lesnick; Susan L. Slager; Esteban Braggio; Tait D. Shanafelt; Neil E. Kay; Stacey M. Fernandes; Jennifer R. Brown; Lili Wang; Shuqiang Li; Kenneth J. Livak; Donna S. Neuberg; Sven Klages; Bernd Timmermann; Thomas J. Kipps; Elias Campo; Andreas Gnirke; Catherine J. Wu; Alexander Meissner
An Autochthonous Mouse Model of Myd88- and BCL2-Driven Diffuse Large B-cell Lymphoma Reveals Actionable Molecular Vulnerabilities
Ruth Flümann; Tim Rehkämper; Pascal Nieper; Pauline Pfeiffer; Alessandra Holzem; Sebastian Klein; Sanil Bhatia; Moritz Kochanek; Ilmars Kisis; Benedikt W. Pelzer; Heinz Ahlert; Julia Hauer; Alexandra da Palma Guerreiro; Jeremy A. Ryan; Maurice Reimann; Arina Riabinska; Janica Wiederstein; Marcus Krüger; Martina Deckert; Janine Altmüller; Andreas R. Klatt; Lukas P. Frenzel; Laura Pasqualucci; Wendy Béguelin; Ari M. Melnick; Sandrine Sander; Manuel Montesinos-Rongen; Anna Brunn; Philipp Lohneis; Reinhard Büttner; Hamid Kashkar; Arndt Borkhardt; Anthony Letai; Thorsten Persigehl; Martin Peifer; Clemens A. Schmitt; Hans Christian Reinhardt; Gero Knittel
A Tumor Suppressor Enhancer of PTEN in T-cell Development and Leukemia
Luca Tottone; Olga Lancho; Jui-Wan Loh; Amartya Singh; Shunsuke Kimura; Juliette Roels; Anna Kuchmiy; Steven Strubbe; Matthew A. Lawlor; Victoria da Silva-Diz; Shirley Luo; Stéphanie Gachet; Carlos A. García-Prieto; Rico Hagelaar; Manel Esteller; Jules P.P. Meijerink; Jean Soulier; Tom Taghon; Pieter Van Vlierberghe; Charles G. Mullighan; Hossein Khiabanian; Pedro P. Rocha; Daniel Herranz
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