Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1
- Author(s)
- Harder, KW; Quilici, C; Naik, E; Inglese, M; Kountouri, N; Turner, A; Zlatic, K; Tarlinton, DM; Hibbs, ML;
- Details
- Publication Year 2004-12-15,Volume 104,Issue #13,Page 3901-3910
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- The Lyn tyrosine kinase plays essential inhibitory signaling roles within hematopoietic cells by recruiting inhibitory phosphatases such as SH2-domain containing phosphatase-1 (SHP-1), SHP-2, and SH2-domain containing 5'-inositol phosphatase (SHIP-1) to the plasma membrane in response to specific stimuli. Lyn-deficient mice display a collection of hematopoietic defects, including autoimmune disease as a result of autoantibody production, and perturbations in myelopoiesis that ultimately lead to splenomegaly and myeloid neoplasia. In this study, we demonstrate that loss of Lyn results in a stem/progenitor cell-intrinsic defect leading to an age-dependent increase in myeloid, erythroid, and primitive hematopoietic progenitor numbers that is independent of autoimmune disease. Despite possessing increased numbers of erythroid progenitors, and a more robust expansion of these cells following phenylhydrazine challenge, Lyn-deficient mice are more severely affected by the chemotherapeutic drug 5-fluorouracil, revealing a greater proportion of cycling progenitors. We also show that mice lacking SHIP-1 have defects in the erythroid and myeloid compartments similar to those in mice lacking Lyn or SHP-1, suggesting an intimate relationship between Lyn, SHP-1, and SHIP-1 in regulating hematopoiesis. (C) 2004 by The American Society of Hematology.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- ERYTHROPOIETIN-INDUCED DIFFERENTIATION; CHRONIC MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; MAST-CELL ACTIVATION; SRC KINASE LYN; NEGATIVE REGULATOR; ERYTHROID-CELLS; MOTH-EATEN; MYELOPROLIFERATIVE DISEASE; STAT5A(-/-)5B(-/-) MICE
- Publisher's Version
- https://doi.org/10.1182/blood-2003-12-4396
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-12-15 12:00:00