title: LYN Kinase in the Tumor Microenvironment Is Essential for the Progression of Chronic Lymphocytic Leukemia.
abstract: Survival of chronic lymphocytic leukemia (CLL) cells strictly depends on the support of an appropriate tumor microenvironment. Here, we demonstrate that LYN kinase is essential for CLL progression. Lyn deficiency results in a significantly reduced CLL burden in vivo. Loss of Lyn within leukemic cells reduces B cell receptor (BCR) signaling including BTK phosphorylation, but surprisingly does not affect leukemic cell expansion. Instead, syngeneic CLL transplantation of CLL cells into Lyn- or Btk-deficient recipients results in a strongly delayed leukemic progression and prolonged survival. Moreover, Lyn deficiency in macrophages hinders nursing functions for CLL cells, which is mediated by direct contact rather than secretion of soluble factors. Taken together, LYN and BTK seem essential for the formation of a microenvironment supporting leukemic growth.
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Phuong-Hien
authors.initials: PH
authors.lastname: Nguyen
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Fedorchenko
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Natascha
authors.initials: N
authors.lastname: Rosen
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Koch
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Barthel
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Winarski
authors.affiliation: Institute of Pathology, University Hospital of Cologne, 50931 Cologne, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Florin
authors.affiliation: Max Planck Institute for Metabolism Research; Institute for Genetics, University of Cologne, 50931 Cologne, Germany.
authors.forename: F Thomas
authors.initials: FT
authors.lastname: Wunderlich
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Reinart
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne-Bonn, CECAD Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, 50931 Cologne, Germany. Electronic address: michael.hallek@uni-koeln.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D015398:Signal Transduction; D059016:Tumor Microenvironment; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases