LYN Kinase in the Tumor Microenvironment Is Essential for the Progression of Chronic Lymphocytic Leukemia.

Phuong-Hien Nguyen, Oleg Fedorchenko, Natascha Rosen, Maximilian Koch, Romy Barthel, Tomasz Winarski, Alexandra Florin, F Thomas Wunderlich, Nina Reinart, Michael Hallek

Cancer cell 2016 Oct 10

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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. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

Phuong-Hien Nguyen, Oleg Fedorchenko, Natascha Rosen, Maximilian Koch, Romy Barthel, Tomasz Winarski, Alexandra Florin, F Thomas Wunderlich, Nina Reinart, Michael Hallek. LYN Kinase in the Tumor Microenvironment Is Essential for the Progression of Chronic Lymphocytic Leukemia. Cancer cell. 2016 Oct 10;30(4):610-622