Flt3

Summary

Gene Symbol: Flt3
Description: FMS-like tyrosine kinase 3
Alias: B230315G04, CD135, Flk-2, Flk2, Flt-3, Ly72, wmfl, receptor-type tyrosine-protein kinase FLT3, FL cytokine receptor, fetal liver kinase 2, tyrosine-protein kinase FLT3, tyrosine-protein kinase receptor flk-2
Species: mouse
Products:     Flt3

Top Publications

  1. Lyman S, James L, Vanden Bos T, de Vries P, Brasel K, Gliniak B, et al. Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. Cell. 1993;75:1157-67 pubmed
    Cloning of a ligand for the murine flt3/flk-2 tyrosine kinase receptor was undertaken using a soluble form of the receptor to identify a source of ligand. A murine T cell line, P7B-0...
  2. Pharr P, Hofbauer A. Loss of flk-2/flt3 expression during commitment of multipotent mouse hematopoietic progenitor cells to the mast cell lineage. Exp Hematol. 1997;25:620-8 pubmed
    The expression of c-kit and flk-2/flt3 was analyzed in various stages of mast cell differentiation using reverse transcriptase polymerase chain reaction (RT-PCR)...
  3. Schwarz B, Sambandam A, Maillard I, Harman B, Love P, Bhandoola A. Selective thymus settling regulated by cytokine and chemokine receptors. J Immunol. 2007;178:2008-17 pubmed
    ..We conclude that fms-like tyrosine kinase receptor-3 signaling is required for the generation of T lineage-competent progenitors, which selectively express molecules, including CCR9, that allow them to settle within the thymus. ..
  4. Kenins L, Gill J, Hollander G, Wodnar Filipowicz A. Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis. Eur J Immunol. 2010;40:81-90 pubmed publisher
    ..After irradiation-induced thymic damage, thymic recovery is facilitated by Flt3 ligand (FL), expressed by perivascular fibroblasts surrounding the thymic entry site of Flt3 receptor-positive ..
  5. Fukuyama Y, King J, Kataoka K, Kobayashi R, Gilbert R, Hollingshead S, et al. A combination of Flt3 ligand cDNA and CpG oligodeoxynucleotide as nasal adjuvant elicits protective secretory-IgA immunity to Streptococcus pneumoniae in aged mice. J Immunol. 2011;186:2454-61 pubmed publisher
    Our previous study showed that a combination of a plasmid-expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotides (CpG ODN) as a combined nasal adjuvant elicited mucosal immune responses in aged (2-y-old) mice...
  6. Sitnicka E, Buza Vidas N, Ahlenius H, Cilio C, Gekas C, Nygren J, et al. Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors. Blood. 2007;110:2955-64 pubmed
    ..Herein, we show that fms-like tyrosine kinase 3 (Flt3) ligand (Fl)-deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and ..
  7. Dehlin M, Andersson S, Erlandsson M, Brisslert M, Bokarewa M. Inhibition of fms-like tyrosine kinase 3 alleviates experimental arthritis by reducing formation of dendritic cells and antigen presentation. J Leukoc Biol. 2011;90:811-7 pubmed publisher
    ..The present study evaluated the role of Flt3 in antigen-induced arthritis. Mice were immunized with mBSA, and arthritis was induced by an i.a. injection of mBSA...
  8. Matthews W, Jordan C, Wiegand G, Pardoll D, Lemischka I. A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell. 1991;65:1143-52 pubmed
    ..Therefore, this receptor may be a key signal transducing component in the totipotent hematopoietic stem cell and its immediate self-renewing progeny. ..
  9. Sambandam A, Maillard I, Zediak V, Xu L, Gerstein R, Aster J, et al. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat Immunol. 2005;6:663-70 pubmed
    ..an immature subset of early T lineage progenitors (ETPs) in the thymus that expressed the tyrosine kinase receptor Flt3 and had preserved B lineage potential at low progenitor frequency...

More Information

Publications88

  1. Brasel K, Escobar S, Anderberg R, de Vries P, Gruss H, Lyman S. Expression of the flt3 receptor and its ligand on hematopoietic cells. Leukemia. 1995;9:1212-8 pubmed
    Expression of the flt3 tyrosine kinase receptor and its ligand were examined on various murine and human hematopoietic cell lines...
  2. Sitnicka E, Bryder D, Theilgaard Monch K, Buza Vidas N, Adolfsson J, Jacobsen S. Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool. Immunity. 2002;17:463-72 pubmed
    ..the first evidence for a nonredundant regulator of this process, in that adult mice deficient in expression of the flt3 ligand (FL) have severely (10-fold) reduced levels of the CLP, accompanied by reductions in the earliest ..
  3. Boyer S, Schroeder A, Smith Berdan S, Forsberg E. All hematopoietic cells develop from hematopoietic stem cells through Flk2/Flt3-positive progenitor cells. Cell Stem Cell. 2011;9:64-73 pubmed publisher
    ..that differentiation into all hematopoietic lineages, including megakaryocyte/erythroid cell types, involves Flk2-expressing non-self-renewing progenitors...
  4. Choudhary C, Brandts C, Schwable J, Tickenbrock L, Sargin B, Ueker A, et al. Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Blood. 2007;110:370-4 pubmed
    Mutations in the receptor tyrosine kinase Flt3 represent a very common genetic lesion in acute myeloid leukemia (AML)...
  5. Brasel K, McKenna H, Charrier K, Morrissey P, Williams D, Lyman S. Flt3 ligand synergizes with granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor to mobilize hematopoietic progenitor cells into the peripheral blood of mice. Blood. 1997;90:3781-8 pubmed
    ..We investigated the capacity of several different growth factors, including human flt3 ligand (FL), alone and in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF ) or ..
  6. Chu S, Heiser D, Li L, Kaplan I, Collector M, Huso D, et al. FLT3-ITD knockin impairs hematopoietic stem cell quiescence/homeostasis, leading to myeloproliferative neoplasm. Cell Stem Cell. 2012;11:346-58 pubmed publisher
    Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) render the receptor constitutively active driving proliferation and survival in leukemic blasts...
  7. Small D, Levenstein M, Kim E, Carow C, Amin S, Rockwell P, et al. STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci U S A. 1994;91:459-63 pubmed
    ..These data suggest that STK-1 may function as a growth factor receptor on hematopoietic stem and/or progenitor cells. ..
  8. Grundler R, Miething C, Thiede C, Peschel C, Duyster J. FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model. Blood. 2005;105:4792-9 pubmed
    Activating mutations of the Fms-like tyrosine kinase 3 (FLT3) receptor are the most common genetic alteration in acute myeloid leukemia (AML)...
  9. Kharazi S, Mead A, Mansour A, Hultquist A, Böiers C, Luc S, et al. Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation. Blood. 2011;118:3613-21 pubmed publisher
    ..Internal tandem duplications (ITDs) of FLT3 occur in approximately 25% cases of acute myeloid leukemia and induce ligand-independent constitutive signaling...
  10. McClanahan T, Culpepper J, Campbell D, Wagner J, Franz Bacon K, Mattson J, et al. Biochemical and genetic characterization of multiple splice variants of the Flt3 ligand. Blood. 1996;88:3371-82 pubmed
    ..performed a comprehensive analysis of cell lines and tissues to compare and contrast the expression patterns of Flt3 ligand (FL), c-Kit ligand (KL), and macrophage colony-stimulating factor as well as their receptors, Flt3, c-Kit, ..
  11. Waskow C, Liu K, Darrasse Jèze G, Guermonprez P, Ginhoux F, Merad M, et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat Immunol. 2008;9:676-83 pubmed publisher
    ..Here we examined the effects of signaling by the receptor tyrosine kinase Flt3 on macrophage DC progenitors in the bone marrow and on peripheral DCs...
  12. Kazi J, Sun J, Phung B, Zadjali F, Flores Morales A, Ronnstrand L. Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3. J Biol Chem. 2012;287:36509-17 pubmed publisher
    The receptor tyrosine kinase Flt3 is an important growth factor receptor in hematopoiesis, and gain-of-function mutations of the receptor contribute to the transformation of acute myeloid leukemia...
  13. Karsunky H, Merad M, Cozzio A, Weissman I, Manz M. Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J Exp Med. 2003;198:305-13 pubmed
    Stimulation of Flt3 receptor tyrosine kinase through its cognate ligand expands early hematopoietic progenitor and dendritic cells (DCs) in humans and mice...
  14. Mackarehtschian K, Hardin J, Moore K, Boast S, Goff S, Lemischka I. Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity. 1995;3:147-61 pubmed
    The flk2 receptor tyrosine kinase has been implicated in hematopoietic development. Mice deficient in flk2 were generated. Mutants developed into healthy adults with normal mature hematopoietic populations...
  15. Whartenby K, Calabresi P, McCadden E, Nguyen B, Kardian D, Wang T, et al. Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc Natl Acad Sci U S A. 2005;102:16741-6 pubmed
    ..A large portion of DCs are derived from hematopoietic progenitors that express FLT3 receptor (CD135), and stimulation of the receptor via FLT3 ligand either in vivo or in vitro is known to drive expansion and ..
  16. Liu K, Victora G, Schwickert T, Guermonprez P, Meredith M, Yao K, et al. In vivo analysis of dendritic cell development and homeostasis. Science. 2009;324:392-7 pubmed publisher
    ..Further cDC development involves cell division, which is controlled in part by regulatory T cells and fms-like tyrosine kinase receptor-3...
  17. Razumovskaya E, Masson K, Khan R, Bengtsson S, Ronnstrand L. Oncogenic Flt3 receptors display different specificity and kinetics of autophosphorylation. Exp Hematol. 2009;37:979-89 pubmed publisher
    Fms-like tyrosine kinase-3 (Flt3), a growth factor receptor normally expressed in hematopoietic progenitor cells, has been shown to have an important role in development of acute myeloid leukemia (AML) due to activating mutations...
  18. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M, et al. Origin of the lamina propria dendritic cell network. Immunity. 2009;31:513-25 pubmed publisher
    ..DCs under the control of macrophage-colony-stimulating factor receptor (M-CSFR) and Fms-like thyrosine kinase 3 (Flt3) ligands...
  19. Lyman S, James L, Escobar S, Downey H, de Vries P, Brasel K, et al. Identification of soluble and membrane-bound isoforms of the murine flt3 ligand generated by alternative splicing of mRNAs. Oncogene. 1995;10:149-57 pubmed
    We have recently described a novel hematopoietic growth factor, referred to as the flt3 ligand, that stimulates the proliferation of sub-populations of hematopoietic cells that are enriched for stem and progenitor cells...
  20. Onai N, Obata Onai A, Tussiwand R, Lanzavecchia A, Manz M. Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development. J Exp Med. 2006;203:227-38 pubmed
    b>Flt3 ligand (Flt3L) is a nonredundant cytokine in type I interferon-producing cell (IPC) and dendritic cell (DC) development, and IPC and DC differentiation potential is confined to Flt3+ hematopoietic progenitor cells...
  21. Lee B, Tothova Z, Levine R, Anderson K, Buza Vidas N, Cullen D, et al. FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell. 2007;12:367-80 pubmed
    Despite their known transforming properties, the effects of leukemogenic FLT3-ITD mutations on hematopoietic stem and multipotent progenitor cells and on hematopoietic differentiation are not well understood...
  22. Darrasse Jèze G, Deroubaix S, Mouquet H, Victora G, Eisenreich T, Yao K, et al. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J Exp Med. 2009;206:1853-62 pubmed publisher
    ..for maintaining normal numbers of dendritic cells (DCs): when T reg cells are depleted, there is a compensatory Flt3-dependent increase in DCs. However, little is known about how T reg cell homeostasis is maintained in vivo...
  23. Carotta S, Dakic A, D Amico A, Pang S, Greig K, Nutt S, et al. The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. Immunity. 2010;32:628-41 pubmed publisher
    ..1 in defined precursors, including the common DC progenitor, blocked Flt3 ligand-induced DC generation in vitro. PU...
  24. Li L, Piloto O, Nguyen H, Greenberg K, Takamiya K, Racke F, et al. Knock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model. Blood. 2008;111:3849-58 pubmed publisher
    Constitutive activation of FMS-like tyrosine kinase 3 (FLT3) by internal tandem duplication (ITD) mutations is one of the most common molecular alterations known in acute myeloid leukemia (AML)...
  25. Elf S, Blevins D, Jin L, Chung T, Williams I, Lee B, et al. p90RSK2 is essential for FLT3-ITD- but dispensable for BCR-ABL-induced myeloid leukemia. Blood. 2011;117:6885-94 pubmed publisher
    ..leukemogenic tyrosine kinases, including BCR-ABL and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)...
  26. Satpathy A, Briseño C, Cai X, Michael D, Chou C, Hsiung S, et al. Runx1 and Cbf? regulate the development of Flt3+ dendritic cell progenitors and restrict myeloproliferative disorder. Blood. 2014;123:2968-77 pubmed publisher
    ..Here, we demonstrate that Cbf? is essential for the development of Flt3(+) macrophage-dendritic cell (DC) progenitors in the bone marrow and all DC subsets in the periphery...
  27. Du N, Pei X, Zhou J, Zhao H, Li X, Fu Y, et al. Transcriptional control of Flt3 ligand targeted by fluorouracil-induced Egr-1 promoter in hematopoietic damage. J Biomed Sci. 2009;16:85 pubmed publisher
    ..Egr-EF, an expression vector pCIneo containing Egr-1 promoter cloned upstream of the cDNA for Flt3 ligand, was used to treat hematopoietic damage...
  28. Varol C, Vallon Eberhard A, Elinav E, Aychek T, Shapira Y, Luche H, et al. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity. 2009;31:502-12 pubmed publisher
    ..Our results highlight the critical importance of the lpDC subset balance for robust gut homeostasis. ..
  29. Mundy Bosse B, Scoville S, Chen L, McConnell K, Mao H, Ahmed E, et al. MicroRNA-29b mediates altered innate immune development in acute leukemia. J Clin Invest. 2016;126:4404-4416 pubmed publisher
    ..These results indicate that leukemic evasion of NK cell surveillance occurs through miR-mediated dysregulation of lymphocyte development, representing an additional mechanism of immune escape in cancer. ..
  30. Meng C, Wang X, Xu Z, Hu M, Liu J, Pan Z, et al. Murine Flt3 ligand-generated plasmacytoid and conventional dendritic cells display functional differentiation in activation, inflammation, and antigen presentation during BCG infection in vitro. In Vitro Cell Dev Biol Anim. 2017;53:67-76 pubmed publisher
    ..We used the murine Fms-like tyrosine kinase 3 (Flt3) ligand to generate conventional DCs (FL-cDCs) and plasmacytoid DCs (FL-pDCs) and further evaluated their ..
  31. Böiers C, Buza Vidas N, Jensen C, Pronk C, Kharazi S, Wittmann L, et al. Expression and role of FLT3 in regulation of the earliest stage of normal granulocyte-monocyte progenitor development. Blood. 2010;115:5061-8 pubmed publisher
    Mice deficient in c-fms-like tyrosine kinase 3 (FLT3) signaling have reductions in early multipotent and lymphoid progenitors, whereas no evident myeloid phenotype has been reported...
  32. Uren A, Kool J, Matentzoglu K, de Ridder J, Mattison J, van Uitert M, et al. Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks. Cell. 2008;133:727-41 pubmed publisher
    ..20 genes that are specifically mutated in either p19(ARF)-deficient, p53-deficient or wild-type mice (including Flt3, mmu-mir-106a-363, Smg6, and Ccnd3), as well as networks of significant collaborative and mutually exclusive ..
  33. Grundler R, Thiede C, Miething C, Steudel C, Peschel C, Duyster J. Sensitivity toward tyrosine kinase inhibitors varies between different activating mutations of the FLT3 receptor. Blood. 2003;102:646-51 pubmed
    Activating mutations of FLT3 have been detected in patients with acute myeloid leukemia (AML)...
  34. Gwin K, Shapiro M, Dolence J, Huang Z, Medina K. Hoxa9 and Flt3 signaling synergistically regulate an early checkpoint in lymphopoiesis. J Immunol. 2013;191:745-54 pubmed publisher
    Hoxa9 and Flt3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow...
  35. Avagyan S, Aguilo F, Kamezaki K, Snoeck H. Quantitative trait mapping reveals a regulatory axis involving peroxisome proliferator-activated receptors, PRDM16, transforming growth factor-?2 and FLT3 in hematopoiesis. Blood. 2011;118:6078-86 pubmed publisher
    ..Here, we show that TGF-?2 specifically and predominantly cell autonomously enhances signaling by FLT3 in vitro and in vivo...
  36. Marhäll A, Heidel F, Fischer T, Rönnstrand L. Internal tandem duplication mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the activation loop D835Y mutation. Ann Hematol. 2018;97:773-780 pubmed publisher
    ..Mutations in FMS-like tyrosine kinase 3 (FLT3) is one of the most prevalent findings in this heterogeneous disease...
  37. Benz C, Martins V, Radtke F, Bleul C. The stream of precursors that colonizes the thymus proceeds selectively through the early T lineage precursor stage of T cell development. J Exp Med. 2008;205:1187-99 pubmed publisher
    ..However, it is clear that of the known intrathymic precursors, only the ETP population contributes significant numbers of T lineage precursors to T cell development. ..
  38. Streeter P, Dudley L, Fleming W. Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation. Exp Hematol. 2003;31:1119-25 pubmed
    ..These results demonstrate that activation of both the Flt-3 and G-CSF receptors provides a high degree of radioprotection to the hematopoietic progenitor cell and stem cell compartment. ..
  39. Bernot K, Nemer J, Santhanam R, Liu S, Zorko N, Whitman S, et al. Eradicating acute myeloid leukemia in a Mll(PTD/wt):Flt3(ITD/wt) murine model: a path to novel therapeutic approaches for human disease. Blood. 2013;122:3778-83 pubmed publisher
    The coexpression of the MLL partial tandem duplication (PTD) and the FLT3 internal tandem duplication (ITD) mutations associate with a poor outcome in cytogenetically normal acute myeloid leukemia (AML)...
  40. Perugini M, Kok C, Brown A, Wilkinson C, Salerno D, Young S, et al. Repression of Gadd45alpha by activated FLT3 and GM-CSF receptor mutants contributes to growth, survival and blocked differentiation. Leukemia. 2009;23:729-38 pubmed publisher
    ..We have identified Gadd45alpha as a downregulated gene in response to constitutive signaling from two FLT3 mutants (FLT3-ITD and FLT3-TKD) commonly found in AML, and a leukemogenic GM-CSF receptor trans-membrane mutant (..
  41. Guermonprez P, Helft J, Claser C, Deroubaix S, Karanje H, Gazumyan A, et al. Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat Med. 2013;19:730-8 pubmed publisher
    ..pathway triggered by Plasmodium infection that regulates dendritic cell homeostasis and adaptive immunity through Flt3 ligand (Flt3l) release...
  42. Yun T, Lee J, Machmach K, Shim D, Choi J, Wi Y, et al. Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells. Cell Metab. 2016;23:852-66 pubmed publisher
    ..Accordingly, pDCs in human atherosclerotic aortas colocalized with Tregs. Collectively, we identified a mechanism of atheroprotection mediated by tolerogenic aortic pDCs. ..
  43. Niki M, Okada H, Takano H, Kuno J, Tani K, Hibino H, et al. Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor. Proc Natl Acad Sci U S A. 1997;94:5697-702 pubmed
    ..Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in the development of definitive hematopoiesis. ..
  44. Reddy P, Sargin B, Choudhary C, Stein S, Grez M, Muller Tidow C, et al. SOCS1 cooperates with FLT3-ITD in the development of myeloproliferative disease by promoting the escape from external cytokine control. Blood. 2012;120:1691-702 pubmed
    Activating mutations in the receptor tyrosine kinase FLT3 are frequently found in acute myelogenous leukemia patients and confer poor clinical prognosis...
  45. McClanahan T, Dalrymple S, Barkett M, Lee F. Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells. Blood. 1993;81:2903-15 pubmed
    ..The defined temporal order for the expression of these genes suggests that they may be useful as markers for multiple stages in the development of different hematopoietic cell lineages during embryogenesis. ..
  46. Sasca D, Hähnel P, Szybinski J, Khawaja K, Kriege O, Pante S, et al. SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia. Blood. 2014;124:121-33 pubmed publisher
    ..In FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)(+)-cells protein, expression of SIRT1 is regulated by FLT3 kinase activity...
  47. Johnson R, Papp E, Grandal I, Kowalski P, Nutter L, Wong R, et al. MuLV-related endogenous retroviral elements and Flt3 participate in aberrant end-joining events that promote B-cell leukemogenesis. Genes Dev. 2014;28:1179-90 pubmed publisher
    ..several cytogenomic approaches, we identified a novel class of activating mutations in Fms-like tyrosine kinase 3 (Flt3), a receptor tyrosine kinase important for normal hematopoiesis in Rag/p53/NHEJ triple-mutant (TM) B-cell leukemias...
  48. Nguyen B, Williams A, Young D, Ma H, Li L, Levis M, et al. FLT3 activating mutations display differential sensitivity to multiple tyrosine kinase inhibitors. Oncotarget. 2017;8:10931-10944 pubmed publisher
    Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that normally functions in hematopoietic cell survival, proliferation and differentiation...
  49. Mkonyi L, Bletsa A, Fristad I, Wiig H, Berggreen E. Importance of lymph vessels in the transcapillary fluid balance in the gingiva studied in a transgenic mouse model. Am J Physiol Heart Circ Physiol. 2010;299:H275-83 pubmed publisher
    ..Our study demonstrates an important role of gingival lymphatics in transcapillary fluid balance in the steady-state condition and during acute perturbations. ..
  50. Salama Y, Hattori K, Heissig B. The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling. Biochem Biophys Res Commun. 2017;490:209-216 pubmed publisher
    ..Mechanistically, we show that Egfl7 overexpression caused Flt3 upregulation in ETPs and thymic ECs, and increased Flt3 ligand plasma elevation in vivo...
  51. Kenins L, Gill J, Boyd R, Hollander G, Wodnar Filipowicz A. Intrathymic expression of Flt3 ligand enhances thymic recovery after irradiation. J Exp Med. 2008;205:523-31 pubmed publisher
    ..thymic immigrant cells and the earliest intrathymic progenitors express the FMS-like tyrosine kinase 3 (Flt3) receptor; however, the functional significance of this expression in the thymus is not known...
  52. Venkatesh D, Park K, Harrington A, Miceli Libby L, Yoon J, Liaw L. Cardiovascular and hematopoietic defects associated with Notch1 activation in embryonic Tie2-expressing populations. Circ Res. 2008;103:423-31 pubmed publisher
    ..Cardiovascular lineages are sensitive to an imbalance in Notch signaling, with aberrant activation reflecting a vascular phenotype comparable to a loss-of-function Notch1 mutation...
  53. Tzelepis K, Koike Yusa H, De Braekeleer E, Li Y, Metzakopian E, Dovey O, et al. A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia. Cell Rep. 2016;17:1193-1205 pubmed publisher
    ..Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies. ..
  54. Beaudin A, Boyer S, Forsberg E. Flk2/Flt3 promotes both myeloid and lymphoid development by expanding non-self-renewing multipotent hematopoietic progenitor cells. Exp Hematol. 2014;42:218-229.e4 pubmed publisher
    ..The function of the receptor tyrosine kinase Flk2 (Flt3) in promoting myeloid development remains poorly defined, despite being commonly mutated in acute myeloid leukemia...
  55. Bailey E, Li L, Duffield A, Ma H, Huso D, Small D. FLT3/D835Y mutation knock-in mice display less aggressive disease compared with FLT3/internal tandem duplication (ITD) mice. Proc Natl Acad Sci U S A. 2013;110:21113-8 pubmed publisher
    FMS-like tyrosine kinase 3 (FLT3) is mutated in approximately one third of acute myeloid leukemia cases...
  56. Hassawi M, Shestakova E, Fournier M, Lebert Ghali C, Vaisson G, Frison H, et al. Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression. Dev Dyn. 2014;243:145-58 pubmed publisher
    ..analysis demonstrated a strong repression of B cell specific genes in these E2A-PBX1/Hoxa9 leukemias in addition to Flt3 activation, indicating inhibition of B cell differentiation in combination with enhanced proliferation...
  57. DeKoter R, Lee H, Singh H. PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity. 2002;16:297-309 pubmed
    ..1 in early B cell development, it is not required. These results demonstrate that PU.1 functions to regulate early B cell development in part by controlling the expression of the IL-7Ralpha gene. ..
  58. Stubbs M, Armstrong S. FLT3 as a therapeutic target in childhood acute leukemia. Curr Drug Targets. 2007;8:703-14 pubmed
    ..Another kinase that has drawn significant attention is the FMS-like tyrosine kinase 3 (FLT3). FLT3 is expressed in most childhood acute leukemias...
  59. Andersson S, Svensson M, Erlandsson M, Dehlin M, Andersson K, Bokarewa M. Activation of Fms-like tyrosine kinase 3 signaling enhances survivin expression in a mouse model of rheumatoid arthritis. PLoS ONE. 2012;7:e47668 pubmed publisher
    ..b>Flt3 ligand (Flt3L) is expressed in the inflamed joints and has adjuvant properties in arthritis...
  60. Abe M, Pelus L, Singh P, Hirade T, Onishi C, Purevsuren J, et al. Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells. PLoS ONE. 2016;11:e0158290 pubmed publisher
    Internal tandem duplication (ITD) mutations in the Fms-related tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML)...
  61. Kamezaki K, Luchsinger L, Snoeck H. Differential requirement for wild-type Flt3 in leukemia initiation among mouse models of human leukemia. Exp Hematol. 2014;42:192-203.e1 pubmed publisher
    b>FLT3 is one of the most frequently mutated genes in acute leukemias. However, the role in leukemogenesis of wild-type (wt) FLT3, which is highly expressed in many hematologic malignancies, is unclear...
  62. Fukuda S, Pelus L. Internal tandem duplication of Flt3 modulates chemotaxis and survival of hematopoietic cells by SDF1alpha but negatively regulates marrow homing in vivo. Exp Hematol. 2006;34:1041-51 pubmed
    We have previously shown that Flt3 ligand (FL)/Flt3 signaling regulates hematopoietic cell migration by modulating the SDF1alpha/CXCR4 signaling pathway...
  63. Karsunky H, Inlay M, Serwold T, Bhattacharya D, Weissman I. Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages. Blood. 2008;111:5562-70 pubmed publisher
    ..can be divided into functionally distinct subsets based on the expression of the tyrosine kinase receptor, Flk2. The Flk2(+) subset contains robust in vivo and in vitro T-cell, B-cell, DC, and NK potential, but lacks myeloid ..
  64. Yang L, Rodriguez B, Mayle A, Park H, Lin X, Luo M, et al. DNMT3A Loss Drives Enhancer Hypomethylation in FLT3-ITD-Associated Leukemias. Cancer Cell. 2016;29:922-934 pubmed publisher
    ..Here, we show that DNMT3A loss synergizes with the FLT3 internal tandem duplication in a dose-influenced fashion to generate rapid lethal lymphoid or myeloid leukemias ..
  65. Huang A, Ju H, Liu K, Zhan G, Liu D, Wen S, et al. Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation. Cancer Lett. 2016;377:149-57 pubmed publisher
    Internal tandem duplication (ITD) of the juxtamembrane region of FMS-like tyrosine kinase-3 (FLT3) receptor is a common type of mutation in adult acute myeloid leukemia (AML), and patient response to FLT3 inhibitors appears to be ..
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    ..a putative receptor-type tyrosine kinase (RTK) was isolated by screening a placenta cDNA library with a mouse Flt3 probe...
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    ..contrast to Tet2 loss, Aid loss does not contribute to enhanced HSC self-renewal or cooperate with Flt3-ITD to induce myeloid transformation...
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    ..of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase...
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    A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L)...
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    ..To detect RAD51 interactions in vivo, we developed a transient nuclear focus assay that was used to demonstrate a complete colocalization of RAB22 with RAD51 in large nuclear foci. ..
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    ..down-regulated megakaryocyte-erythroid (MkE) potential are restricted to cells with high levels of cell-surface FLT3 expression, whereas HSCs and MkE progenitors lack detectable cell-surface FLT3...
  72. Rottapel R, Turck C, Casteran N, Liu X, Birnbaum D, Pawson T, et al. Substrate specificities and identification of a putative binding site for PI3K in the carboxy tail of the murine Flt3 receptor tyrosine kinase. Oncogene. 1994;9:1755-65 pubmed
    b>Flt3 is a receptor tyrosine kinase (RTK) structurally related to the CSF-1R encoded by the c-fms locus, Kit and the PDGFR which is restricted in its expression to hematopoietic precursor populations and several distinct cell types within ..
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    ..The receptor tyrosine kinase FLT3 is of importance for proliferation, survival and differentiation of hematopoietic cells and is frequently mutated ..
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    ..disease which progresses to leukemia and involves hematopoietic progenitors that exhibit augmented FLT3 signaling. Suppressing this signaling through matings with FLT3 ligand knockout mice prevents leukemia development...
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    FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations resulting in constitutive kinase activity are common in acute myeloid leukemia (AML) and carry a poor prognosis...
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    ..The development of NH cells depends on the cytokine receptor Flt3, which is required for the efficient generation of bone marrow lymphoid progenitors...
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    The internal tandem duplication (ITD) mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor found in acute myeloid leukemia patients are associated with poor prognosis...
  78. Maroc N, Rottapel R, Rosnet O, Marchetto S, Lavezzi C, Mannoni P, et al. Biochemical characterization and analysis of the transforming potential of the FLT3/FLK2 receptor tyrosine kinase. Oncogene. 1993;8:909-18 pubmed
    We recently cloned an additional member of the receptor type tyrosine kinase class III. This new gene, called Flt3 by our group [Rosnet, O., Matteï, M.G., Marchetto, S. & Birnbaum, D. (1991). Genomics, 9, 380-385; Rosnet, O...
  79. Bozzacco L, Trumpfheller C, Huang Y, Longhi M, Shimeliovich I, Schauer J, et al. HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC. Eur J Immunol. 2010;40:36-46 pubmed publisher
    ..These findings support future experiments to use Flt3L to enhance presentation of DC-targeted vaccines. ..