FLT3

Summary

Gene Symbol: FLT3
Description: fms related tyrosine kinase 3
Alias: CD135, FLK-2, FLK2, STK1, receptor-type tyrosine-protein kinase FLT3, CD135 antigen, FL cytokine receptor, fetal liver kinase 2, fms-like tyrosine kinase 3, growth factor receptor tyrosine kinase type III, stem cell tyrosine kinase 1
Species: human
Products:     FLT3

Top Publications

  1. Schlenk R, Dohner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909-18 pubmed publisher
    ..normal acute myeloid leukemia (AML) cells: the nucleophosmin gene (NPM1), the fms-related tyrosine kinase 3 gene (FLT3), the CCAAT/enhancer binding protein alpha gene (CEPBA), the myeloid-lymphoid or mixed-lineage leukemia gene (MLL), ..
  2. Braoudaki M, Karpusas M, Katsibardi K, Papathanassiou C, Karamolegou K, Tzortzatou Stathopoulou F. Frequency of FLT3 mutations in childhood acute lymphoblastic leukemia. Med Oncol. 2009;26:460-2 pubmed publisher
    b>FLT3 mutations are occasionally observed in acute lymphoblastic leukemia (ALL). These most frequently manifest as internal tandem duplications (ITD) and activation loop (AL) mutations...
  3. Heiss E, Masson K, Sundberg C, Pedersen M, Sun J, Bengtsson S, et al. Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2. Blood. 2006;108:1542-50 pubmed
    Early signal relay steps upon ligand binding to the receptor tyrosine kinase Flt3 (ie, sites of Flt3 autophosphorylation and subsequent docking partners) are mainly unresolved...
  4. Polzer H, Janke H, Schmid D, Hiddemann W, Spiekermann K. Casitas B-lineage lymphoma mutants activate AKT to induce transformation in cooperation with class III receptor tyrosine kinases. Exp Hematol. 2013;41:271-80.e4 pubmed publisher
    ..predominantly cooperates with receptor tyrosine kinase (RTK) class III receptors (PDGFRA, PDGFRB, KIT, and FLT3), but not with non-class III RTKs or cytokine receptors, to induce IL-3-independent growth of Ba/F3 cells...
  5. Andersson A, Paulsson K, Lilljebjörn H, Lassen C, Strombeck B, Heldrup J, et al. FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns. Genes Chromosomes Cancer. 2008;47:64-70 pubmed
    ..internal tandem duplications (ITD) and activating point mutations in the second tyrosine kinase domain (ATKD) of FLT3. Seventeen (10%) FLT3 mutations (6 ITD, 11 ATKD; mutually exclusive) were detected...
  6. Kornblau S, Minden M, Rosen D, Putta S, Cohen A, Covey T, et al. Dynamic single-cell network profiles in acute myelogenous leukemia are associated with patient response to standard induction therapy. Clin Cancer Res. 2010;16:3721-33 pubmed publisher
    ..In patients > or =60 years old, nonresponse was associated with FLT3 ligand-mediated increase in phosphorylated Akt and phosphorylated extracellular signal-regulated kinase...
  7. 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...
  8. Yoo S, Park C, Jang S, Seo E, Lee K, Chi H. Inferior prognostic outcome in acute promyelocytic leukemia with alterations of FLT3 gene. Leuk Lymphoma. 2006;47:1788-93 pubmed
    Alterations of the FLT3 gene, in the form of internal tandem duplications (ITD) and D835 point mutations, occur frequently in acute promyelocytic leukemia (APL)...
  9. Weisberg E, Banerji L, Wright R, Barrett R, Ray A, Moreno D, et al. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells. Blood. 2008;111:3723-34 pubmed publisher
    ..the ability of BAG956, a dual PI3K/PDK-1 inhibitor, to be used in combination with inhibitors of BCR-ABL and mutant FLT3, as well as with the mTOR inhibitor, rapamycin, and the rapamycin derivative, RAD001...

More Information

Publications76

  1. Fathi A, Levis M. FLT3 inhibitors: a story of the old and the new. Curr Opin Hematol. 2011;18:71-6 pubmed publisher
    Ever since the recognition that FMS-like tyrosine kinase 3 (FLT3) mutations exert a profound negative prognostic impact on the clinical outcome of patients with acute myeloid leukemia (AML), researchers have sought to find effective small-..
  2. Paschka P, Marcucci G, Ruppert A, Whitman S, Mrozek K, Maharry K, et al. Wilms' tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol. 2008;26:4595-602 pubmed publisher
    ..The patients also were assessed for the presence of FLT3 internal tandem duplications (FLT3-ITD), FLT3 tyrosine kinase domain mutations (FLT3-TKD), MLL partial tandem ..
  3. Davidsson J, Paulsson K, Lindgren D, Lilljebjörn H, Chaplin T, Forestier E, et al. Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations. Leukemia. 2010;24:924-31 pubmed publisher
    ..11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution ..
  4. Whitman S, Ruppert A, Radmacher M, Mrozek K, Paschka P, Langer C, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008;111:1552-9 pubmed
    The prognostic relevance of FLT3 D835/I836 mutations (FLT3-TKD) in cytogenetically normal acute myeloid leukemia (CN-AML) remains to be established...
  5. Meshinchi S, Appelbaum F. Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin Cancer Res. 2009;15:4263-9 pubmed publisher
    ..Ligand-induced stimulation of the FMS-like tyrosine kinase 3 (FLT3) leads to activation of multiple downstream effector pathways resulting in differentiation and proliferation of ..
  6. Sargin B, Choudhary C, Crosetto N, Schmidt M, Grundler R, Rensinghoff M, et al. Flt3-dependent transformation by inactivating c-Cbl mutations in AML. Blood. 2007;110:1004-12 pubmed
    In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine kinase (RTK) Flt3 is frequently involved in leukemic transformation. However, little is known about a possible role of highly expressed wild-type Flt3 in AML...
  7. Bornhauser M, Illmer T, Schaich M, Soucek S, Ehninger G, Thiede C. Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML. Blood. 2007;109:2264-5; author reply 2265 pubmed
  8. Mead A, Linch D, Hills R, Wheatley K, Burnett A, Gale R. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood. 2007;110:1262-70 pubmed
    The prognostic impact of tyrosine kinase domain (TKD) mutations of the fms-like tyrosine kinase-3 (FLT3) gene in acute myeloid leukemia (AML) is currently uncertain...
  9. Irish J, Anensen N, Hovland R, Skavland J, Børresen Dale A, Bruserud O, et al. Flt3 Y591 duplication and Bcl-2 overexpression are detected in acute myeloid leukemia cells with high levels of phosphorylated wild-type p53. Blood. 2007;109:2589-96 pubmed
    ..Within those patients with the highest levels of Bcl-2 expression, we identified a mutation in FLT3 that duplicated phosphorylation site Y591...
  10. Meshinchi S, Stirewalt D, Alonzo T, Boggon T, Gerbing R, Rocnik J, et al. Structural and numerical variation of FLT3/ITD in pediatric AML. Blood. 2008;111:4930-3 pubmed publisher
    b>FLT3 internal tandem duplication (FLT3/ITD) is a common somatic mutation in acute myeloid leukemia (AML) with significant variation in the position, length, and number of duplications of the FLT3 gene...
  11. Yoshimoto G, Miyamoto T, Jabbarzadeh Tabrizi S, Iino T, Rocnik J, Kikushige Y, et al. FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation. Blood. 2009;114:5034-43 pubmed publisher
    ..hematopoietic stem cells (HSCs) express MCL-1 at the highest level in response to FMS-like tyrosine kinase-3 (FLT3) signaling...
  12. Oshikawa G, Nagao T, Wu N, Kurosu T, Miura O. c-Cbl and Cbl-b ligases mediate 17-allylaminodemethoxygeldanamycin-induced degradation of autophosphorylated Flt3 kinase with internal tandem duplication through the ubiquitin proteasome pathway. J Biol Chem. 2011;286:30263-73 pubmed publisher
    The class III receptor-tyrosine kinase Flt3 regulates normal hematopoiesis...
  13. Masson K, Ronnstrand L. Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3. Cell Signal. 2009;21:1717-26 pubmed publisher
    ..Here we discuss the hematopoietic growth factor receptors c-Kit and Flt3 and their downstream signaling in normal as well as malignant cells...
  14. Schmidt Arras D, Böhmer S, Koch S, Müller J, Blei L, Cornils H, et al. Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality. Blood. 2009;113:3568-76 pubmed publisher
    The mechanism of cell transformation by Fms-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia (AML) is incompletely understood...
  15. Syampurnawati M, Tatsumi E, Furuta K, Takenokuchi M, Nakamachi Y, Kawano S, et al. HLA-DR-negative AML (M1 and M2): FLT3 mutations (ITD and D835) and cell-surface antigen expression. Leuk Res. 2007;31:921-9 pubmed
    b>FLT3 mutations and cell-surface antigen were investigated in 29 DR-negative (DR(-)) M1/M2 AML samples in comparison with 30 DR-positive (DR(+)) M1/M2 AML samples. FLT3-ITD was detected in 59.3% and D835 was detected in 7.4% of the samples...
  16. Ley T, Ding L, Walter M, McLellan M, Lamprecht T, Larson D, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363:2424-33 pubmed publisher
    ..mutations were associated with adverse outcomes among patients with an intermediate-risk cytogenetic profile or FLT3 mutations, regardless of age, and were independently associated with a poor outcome in Cox proportional-hazards ..
  17. Schnittger S, Bacher U, Kern W, Alpermann T, Haferlach C, Haferlach T. Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia. Leukemia. 2011;25:1297-304 pubmed publisher
    High FLT3-ITD/wildtype (wt) load in FLT3-ITD-mutated AML has been associated with adverse impact on outcome in several studies...
  18. Williams L, Kelley H, Meng X, Prada A, Crisan D. FLT3 mutations in myeloproliferative neoplasms: the Beaumont experience. Diagn Mol Pathol. 2013;22:156-60 pubmed publisher
    b>FLT3 is one of the most frequently mutated genes in acute myeloid leukemia. Previous studies have reported FLT3 mutation in as many as 9...
  19. Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients. Blood. 2008;111:2527-37 pubmed
    We characterized the mutational status of the FLT3 tyrosine kinase domain (FLT3-TLD) in 3082 patients with newly diagnosed AML. FLT3-TKD mutations were detected in 147 of 3082 (4.8%) patients...
  20. Breitenbuecher F, Schnittger S, Grundler R, Markova B, Carius B, Brecht A, et al. Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor. Blood. 2009;113:4074-7 pubmed publisher
    In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of the juxtamembrane (JM) of FLT3 have been shown to play a crucial role in driving proliferation and survival of the leukemic clone...
  21. Kikushige Y, Yoshimoto G, Miyamoto T, Iino T, Mori Y, Iwasaki H, et al. Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. J Immunol. 2008;180:7358-67 pubmed
    b>FLT3/FLK2, a member of the receptor tyrosine kinase family, plays a critical role in maintenance of hematopoietic homeostasis, and the constitutively active form of the FLT3 mutation is one of the most common genetic abnormalities in ..
  22. Ortlepp C, Steudel C, Heiderich C, Koch S, Jacobi A, Ryser M, et al. Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. Exp Hematol. 2013;41:444-461.e4 pubmed publisher
    ..functionally active in acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) mutation of the FLT3 receptor gene...
  23. Sallmyr A, Fan J, Datta K, Kim K, Grosu D, Shapiro P, et al. Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML. Blood. 2008;111:3173-82 pubmed publisher
    Activating mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor occur in approximately 30% of acute myeloid leukemia (AML) patients and, at least for internal tandem duplication (ITD) mutations, are associated with poor prognosis...
  24. Bachas C, Schuurhuis G, Hollink I, Kwidama Z, Goemans B, Zwaan C, et al. High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine. Blood. 2010;116:2752-8 pubmed publisher
    ..mutations at either stage of the disease, mutation status changed between diagnosis and relapse, particularly in FLT3, WT1, and RAS genes...
  25. Rosen D, Minden M, Kornblau S, Cohen A, Gayko U, Putta S, et al. Functional characterization of FLT3 receptor signaling deregulation in acute myeloid leukemia by single cell network profiling (SCNP). PLoS ONE. 2010;5:e13543 pubmed publisher
    Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem ..
  26. Ravandi F, Kantarjian H, Faderl S, Garcia Manero G, O Brien S, Koller C, et al. Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse. Leuk Res. 2010;34:752-6 pubmed publisher
    Mutations of Fms-like tyrosine kinase-3 (FLT3) have been described in about 30% of patients with acute myeloid leukemia (AML) and are associated with a shorter disease-free and overall survival after initial therapy...
  27. Carbuccia N, Trouplin V, Gelsi Boyer V, Murati A, Rocquain J, Adelaide J, et al. Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia. 2010;24:469-73 pubmed publisher
  28. Fan J, Li L, Small D, Rassool F. Cells expressing FLT3/ITD mutations exhibit elevated repair errors generated through alternative NHEJ pathways: implications for genomic instability and therapy. Blood. 2010;116:5298-305 pubmed publisher
    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...
  29. Stubbs M, Kim Y, Krivtsov A, Wright R, Feng Z, Agarwal J, et al. MLL-AF9 and FLT3 cooperation in acute myelogenous leukemia: development of a model for rapid therapeutic assessment. Leukemia. 2008;22:66-77 pubmed
    ..HRX, ALL-1) gene possess high-level expression, and frequent activating mutations of the receptor tyrosine kinase FLT3. We used a murine bone marrow transplant model to assess cooperation between MLL translocation and FLT3 activation...
  30. Williams A, Nguyen B, Li L, Brown P, Levis M, Leahy D, et al. Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors. Leukemia. 2013;27:48-55 pubmed publisher
    FMS-like tyrosine kinase 3 (FLT3) normally functions in the survival/proliferation of hematopoietic stem/progenitor cells, but its constitutive activation by internal tandem duplication (ITD) mutations correlates with a poor prognosis in ..
  31. Bains A, Luthra R, Medeiros L, Zuo Z. FLT3 and NPM1 mutations in myelodysplastic syndromes: Frequency and potential value for predicting progression to acute myeloid leukemia. Am J Clin Pathol. 2011;135:62-9 pubmed publisher
    We reviewed FLT3 and NPM1 mutation data in a large cohort of patients with myelodysplastic syndrome (MDS). The frequencies of FLT3 and NPM1 mutation were 2.0% and 4...
  32. Colovic N, Tosic N, Aveic S, Djuric M, Milic N, Bumbasirevic V, et al. Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia. Ann Hematol. 2007;86:741-7 pubmed
    Mutations in the fms-like tyrosine kinase 3 (FLT3) gene, such as internal tandem duplication (FLT3/ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are the most common abnormalities in acute myeloid ..
  33. Hoehn D, Medeiros L, Chen S, Tian T, Jorgensen J, Ahmed Y, et al. CD117 expression is a sensitive but nonspecific predictor of FLT3 mutation in T acute lymphoblastic leukemia and T/myeloid acute leukemia. Am J Clin Pathol. 2012;137:213-9 pubmed publisher
    Others have suggested that CD117, or an immunophenotypic profile including CD117, can serve as surrogate for FLT3 mutation in T acute lymphoblastic leukemia (ALL), thereby guiding targeted therapy...
  34. Schittenhelm M, Yee K, Tyner J, McGreevey L, Haley A, Town A, et al. FLT3 K663Q is a novel AML-associated oncogenic kinase: Determination of biochemical properties and sensitivity to Sunitinib (SU11248). Leukemia. 2006;20:2008-14 pubmed
    Somatic mutations of FLT3 resulting in constitutive kinase activation are the most common acquired genomic abnormality found in acute myeloid leukemia (AML)...
  35. Gale R, Green C, Allen C, Mead A, Burnett A, Hills R, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008;111:2776-84 pubmed
    An internal tandem duplication in the fms-like tyrosine kinase 3 gene (FLT3/ITD) is associated with poor prognosis in acute myeloid leukemia (AML), but the impact of mutant level, size, and interaction with nucleophosmin 1 (NPM1) ..
  36. Boonthimat C, Thongnoppakhun W, Auewarakul C. Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations. Haematologica. 2008;93:1565-9 pubmed publisher
    ..b>FLT3 mutation was more frequent in mutant NPM1 than wild-type cases (56.8% vs. 25...
  37. Ghosh K, Swaminathan S, Madkaikar M, Gupta M, Kerketta L, Vundinti B. FLT3 and NPM1 mutations in a cohort of AML patients and detection of a novel mutation in tyrosine kinase domain of FLT3 gene from Western India. Ann Hematol. 2012;91:1703-12 pubmed publisher
    ..Several novel molecular genetic aberrations in FLT3 and NPM1 have been shown to have a prognostic impact in AML, particularly in those having normal karyotype...
  38. Hou H, Chou W, Lin L, Chen C, Tang J, Tseng M, et al. Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. Leukemia. 2008;22:1075-8 pubmed
  39. Paulsson K, Horvat A, Strombeck B, Nilsson F, Heldrup J, Behrendtz M, et al. Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2008;47:26-33 pubmed
    Although it has been suggested that mutations of the FLT3, NRAS, KRAS, and PTPN11 genes are particularly frequent in high hyperdiploid (>50 chromosomes) pediatric acute lymphoblastic leukemias (ALLs), this has as yet not been confirmed ..
  40. Ishikawa Y, Kiyoi H, Tsujimura A, Miyawaki S, Miyazaki Y, Kuriyama K, et al. Comprehensive analysis of cooperative gene mutations between class I and class II in de novo acute myeloid leukemia. Eur J Haematol. 2009;83:90-8 pubmed publisher
    ..We comprehensively analyzed the FLT3, cKIT, N-RAS, C/EBPA, AML1, MLL, NPM1, and TP53 mutations in 144 newly diagnosed de novo AML...
  41. Beitinjaneh A, Jang S, Roukoz H, Majhail N. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations in acute promyelocytic leukemia: a systematic review. Leuk Res. 2010;34:831-6 pubmed publisher
    The fms-like tyrosine kinase 3 (FLT3) gene aberrations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, are frequent in acute promyelocytic leukemia (APL)...
  42. Ravandi F, Cortes J, Jones D, Faderl S, Garcia Manero G, Konopleva M, et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010;28:1856-62 pubmed publisher
    ..have achieved a complete remission (CR), including 14 (93%) of 15 patients with mutated FMS-like tyrosine kinase-3 (FLT3; the 15th patient had complete remission with incomplete platelet recovery [CRp]) and 24 (66%) of 36 patients with ..
  43. Renneville A, Boissel N, Zurawski V, Llopis L, Biggio V, Nibourel O, et al. Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia: a study from the Acute Leukemia French Association. Cancer. 2009;115:3719-27 pubmed publisher
    ..The patients also were assessed for the presence of the fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD), FLT3-D835/I836, nucleophosmin 1 (NPM1), and CCAAT/enhancer binding protein alpha (CEBPA) mutations...
  44. Dunna N, Rajappa S, Digumarti R, Vure S, Kagita S, Damineni S, et al. Fms like tyrosine kinase (FLT3) and nucleophosmin 1 (NPM1) mutations in de novo normal karyotype acute myeloid leukemia (AML). Asian Pac J Cancer Prev. 2010;11:1811-6 pubmed
    Mutations in FLT3 and NPM1 are important prognostic factors in AML, influencing outcome in normal karyotype cases...
  45. Pinheiro R, de Sá Moreira E, Silva M, Alberto F, Chauffaille M. FLT3 internal tandem duplication during myelodysplastic syndrome follow-up: a marker of transformation to acute myeloid leukemia. Cancer Genet Cytogenet. 2008;183:89-93 pubmed publisher
    ..Some molecular abnormalities related to acute myeloid leukemia (AML) transformation have been reported, such as FLT3 (FMS-like tyrosine kinase 3) mutations...
  46. Sanz M, Burnett A, Lo Coco F, Lowenberg B. FLT3 inhibition as a targeted therapy for acute myeloid leukemia. Curr Opin Oncol. 2009;21:594-600 pubmed publisher
    ..The tyrosine kinase receptor FLT3 plays an important role in the survival and proliferation of blasts, and approximately 25% of patients with AML ..
  47. 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...
  48. Daver N, Strati P, Jabbour E, Kadia T, Luthra R, Wang S, et al. FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia. Am J Hematol. 2013;88:56-9 pubmed publisher
    FMS-like tyrosine kinase III (FLT3) mutations occur in one-third of acute myeloid leukemia (AML) patients and predict poor outcome...
  49. Moore A, Faisal A, Gonzalez De Castro D, Bavetsias V, Sun C, Atrash B, et al. Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns. Leukemia. 2012;26:1462-70 pubmed publisher
    Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD(+) acute myeloid leukaemia (AML)...
  50. Odgerel T, Kikuchi J, Wada T, Shimizu R, Futaki K, Kano Y, et al. The FLT3 inhibitor PKC412 exerts differential cell cycle effects on leukemic cells depending on the presence of FLT3 mutations. Oncogene. 2008;27:3102-10 pubmed
    PKC412 is a staurosporine derivative that inhibits several protein kinases including FLT3, and is highly anticipated as a novel therapeutic agent for acute myeloblastic leukemia (AML) carrying FLT3 mutations...
  51. Lierman E, Lahortiga I, Van Miegroet H, Mentens N, Marynen P, Cools J. The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. Haematologica. 2007;92:27-34 pubmed
    ..investigated the efficacy of sorafenib at inhibiting mutants of the receptor tyrosine kinases PDGFRbeta, KIT, and FLT3, which are implicated in the pathogenesis of myeloid malignancies...
  52. Arora D, Stopp S, Böhmer S, Schons J, Godfrey R, Masson K, et al. Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling. J Biol Chem. 2011;286:10918-29 pubmed publisher
    Fms-like tyrosine kinase 3 (FLT3) plays an important role in hematopoietic differentiation, and constitutively active FLT3 mutant proteins contribute to the development of acute myeloid leukemia...
  53. Wagner K, Damm F, Thol F, Göhring G, Gorlich K, Heuser M, et al. FLT3-internal tandem duplication and age are the major prognostic factors in patients with relapsed acute myeloid leukemia with normal karyotype. Haematologica. 2011;96:681-6 pubmed publisher
    ..Leukemic blasts were analyzed at diagnosis for genetic aberrations in the FLT3, NPM1, CEBPA, WT1, IDH1 and IDH2 genes by polymerase chain reaction and/or direct sequencing...
  54. De Vries A, Stam R, Schneider P, Niemeyer C, van Wering E, Haas O, et al. Role of mutation independent constitutive activation of FLT3 in juvenile myelomonocytic leukemia. Haematologica. 2007;92:1557-60 pubmed
    b>FLT3 gene mutations have been identified as prognostic factors in myeloid malignancies. Furthermore, FLT3 can be activated by wild type overexpression or ligand-dependent in leukemic cells co-expressing FLT3 ligand (FLT3L)...
  55. Smith C, Lasater E, Zhu X, Lin K, Stewart W, Damon L, et al. Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD. Blood. 2013;121:3165-71 pubmed publisher
    Secondary point mutations in the Fms-like tyrosine kinase 3 (FLT3) tyrosine kinase domain (KD) are common causes of acquired clinical resistance to the FLT3 inhibitors AC220 (quizartinib) and sorafenib...
  56. Kayser S, Schlenk R, Londono M, Breitenbuecher F, Wittke K, Du J, et al. Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood. 2009;114:2386-92 pubmed publisher
    ..tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD-positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic ..
  57. Akagi T, Ogawa S, Dugas M, Kawamata N, Yamamoto G, Nannya Y, et al. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype. Haematologica. 2009;94:213-23 pubmed publisher
    ..Importantly, 12 patients (32%) had copy-number neutral loss of heterozygosity, causing duplication of either mutant FLT3 (2 cases), JAK2 (1 case) or AML1/RUNX1 (1 case); and each had loss of the normal allele...
  58. Godfrey R, Arora D, Bauer R, Stopp S, Müller J, Heinrich T, et al. Cell transformation by FLT3 ITD in acute myeloid leukemia involves oxidative inactivation of the tumor suppressor protein-tyrosine phosphatase DEP-1/ PTPRJ. Blood. 2012;119:4499-511 pubmed publisher
    Signal transduction of FMS-like tyrosine kinase 3 (FLT3) is regulated by protein-tyrosine phosphatases (PTPs). We recently identified the PTP DEP-1/CD148/PTPRJ as a novel negative regulator of FLT3...
  59. Pollard J, Alonzo T, Gerbing R, Woods W, Lange B, Sweetser D, et al. FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome in acute myeloid leukemia. Blood. 2006;108:2764-9 pubmed
    ..Using FLT3 internal tandem duplication (FLT3/ITD) as a molecular marker, we tested the hypothesis that clinical outcome in AML ..
  60. Seedhouse C, Grundy M, Shang S, Ronan J, Pimblett H, Russell N, et al. Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine. Clin Cancer Res. 2009;15:7291-8 pubmed publisher
    Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease...
  61. Schneider F, Hoster E, Unterhalt M, Schneider S, Dufour A, Benthaus T, et al. The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype. Blood. 2012;119:4383-6 pubmed publisher
    The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele...
  62. Fröhling S, Scholl C, Levine R, Loriaux M, Boggon T, Bernard O, et al. Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles. Cancer Cell. 2007;12:501-13 pubmed
    Mutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but it is not known whether alterations outside these regions contribute to leukemogenesis...
  63. Rausei Mills V, Chang K, Gaal K, Weiss L, Huang Q. Aberrant expression of CD7 in myeloblasts is highly associated with de novo acute myeloid leukemias with FLT3/ITD mutation. Am J Clin Pathol. 2008;129:624-9 pubmed publisher
    ..Previous studies have suggested that the Fms-like tyrosine kinase-3 internal tandem duplication (FLT3/ITD) mutation-positive de novo AML may represent a distinctive subgroup of AML...
  64. Green C, Koo K, Hills R, Burnett A, Linch D, Gale R. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol. 2010;28:2739-47 pubmed publisher
    ..CEBPA-double patients had evidence of a lower coincidence with FLT3/ITDs (P = .04) and were highly unlikely to have an NPM1 mutation (P < .0001)...
  65. Chauhan P, Bhushan B, Mishra A, Singh L, Saluja S, Verma S, et al. Mutation of FLT3 gene in acute myeloid leukemia with normal cytogenetics and its association with clinical and immunophenotypic features. Med Oncol. 2011;28:544-51 pubmed publisher
    ..Activating mutations on FLT3 receptor are one of the most common genetic alterations reported...
  66. Zhou J, Bi C, Chng W, Cheong L, Liu S, Mahara S, et al. PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-AML therapy. PLoS ONE. 2011;6:e19798 pubmed publisher
    Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic...
  67. Zaker F, Mohammadzadeh M, Mohammadi M. Detection of KIT and FLT3 mutations in acute myeloid leukemia with different subtypes. Arch Iran Med. 2010;13:21-5 pubmed
    ..The presence of fms-like tyrosine kinase 3 was significantly associated with M3 morphology and mutations of KIT were significantly associated with M2 and M4 subtypes. ..