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CD135

January 01, 1970

Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3 with fms standing for "feline McDonough sarcoma"), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).

FLT3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFLT3, CD135, FLK-2, FLK2, STK1, fms related tyrosine kinase 3, fms related receptor tyrosine kinase 3
External IDsOMIM: 136351 MGI: 95559 HomoloGene: 3040 GeneCards: FLT3
Orthologs
SpeciesHumanMouse
Entrez

2322

14255

Ensembl

ENSG00000122025

ENSMUSG00000042817

UniProt

P36888

Q00342

RefSeq (mRNA)

NM_004119

NM_010229

RefSeq (protein)

NP_004110

NP_034359

Location (UCSC)Chr 13: 28 – 28.1 MbChr 5: 147.27 – 147.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

It is expressed on the surface of many hematopoietic progenitor cells. Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells.

The FLT3 gene is one of the most frequently mutated genes in acute myeloid leukemia (AML).[5] High levels of wild-type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations. These high levels may be associated with worse prognosis.

Structure edit

FLT3 is composed of five extracellular immunoglobulin-like domains, an extracellular domain, a transmembrane domain, a juxtamembrane domain and a tyrosine-kinase domain consisting of 2 lobes that are connected by a tyrosine-kinase insert. Cytoplasmic FLT3 undergoes glycosylation, which promotes localization of the receptor to the membrane.[6]

Function edit

CD135 is a class III receptor tyrosine kinase. When this receptor binds to FLT3L a ternary complex is formed in which two FLT3 molecules are bridged by one (homodimeric) FLT3L.[7] The formation of such complex brings the two intracellular domains in close proximity to each other, eliciting initial trans-phosphorylation of each kinase domain. This initial phosphorylation event further activates the intrinsic tyrosine kinase activity, which in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. Signaling through CD135 plays a role in cell survival, proliferation, and differentiation. CD135 is important for lymphocyte (B cell and T cell) development.

Two cytokines that down modulate FLT3 activity (& block FLT3-induced hematopoietic activity) are:

TGF-beta especially, decreases FLT3 protein levels and reverses the FLT3L-induced decrease in the time that hematopoietic progenitors spend in the G1-phase of the cell cycle.[6]

Clinical significance edit

Cell surface marker edit

Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. In mice, CD135 is expressed on several hematopoietic (blood) cells, including long- and short-term reconstituting hematopoietic stem cells (HSC) and other progenitors like multipotent progenitors (MPPs) and common lymphoid progenitors (CLP).[8]

Role in cancer edit

CD135 is a proto-oncogene, meaning that mutations of this protein can lead to cancer.[9] Mutations of the FLT3 receptor can lead to the development of leukemia, a cancer of bone marrow hematopoietic progenitors. Internal tandem duplications of FLT3 (FLT3-ITD) are the most common mutations associated with acute myelogenous leukemia (AML) and are a prognostic indicator associated with adverse disease outcome.

FLT3 inhibitors edit

Gilteritinib, a dual FLT3-AXL tyrosine kinase inhibitor[10] has completed a phase 3 trial of relapsed/refractory acute myeloid leukemia in patients with FLT3 ITD or TKD mutations.[11] In 2017, gilteritinib gained FDA orphan drug status for AML.[12] In November 2018, the FDA approved gilteritinib (Xospata) for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.[13]

In July 2023, quizartinib (Vanflyta) was also approved for the treatment of newly diagnosed AML with FLT3 internal tandem duplication (ITD)-positive, as detected by an FDA-approved test.[14] Precisely, it should be used with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy.[14]

Midostaurin was approved by the FDA in April 2017 for the treatment of adult patients with newly diagnosed AML who are positive for oncogenic FLT3, in combination with chemotherapy.[15] The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML.

Sorafenib has been reported to show significant activity against Flt3-ITD positive acute myelogenous leukemia.[16][17]

Sunitinib also inhibits Flt3.

Lestaurtinib is in clinical trials.

A paper published in Nature in April 2012 studied patients who developed resistance to FLT3 inhibitors, finding specific DNA sites contributing to that resistance and highlighting opportunities for future development of inhibitors that could take into account the resistance-conferring mutations for a more potent treatment.[18]

See also edit

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000122025 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042817 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Yagasaki F, Shimazaki C, Akiyama H, Saito K, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Saito H, Ueda R, Ohno R, Naoe T (April 2001). "Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies". Blood. 97 (8): 2434–9. doi:10.1182/blood.V97.8.2434. PMID 11290608.
  6. ^ a b . Pathway Central. SABiosciences. Archived from the original on 2017-11-11. Retrieved 2012-12-18.
  7. ^ Verstraete K, Vandriessche G, Januar M, Elegheert J, Shkumatov AV, Desfosses A, Van Craenenbroeck K, Svergun DI, Gutsche I, Vergauwen B, Savvides SN (February 2011). "Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex". Blood. 118 (1): 60–68. doi:10.1182/blood-2011-01-329532. PMID 21389326.
  8. ^ Mooney CJ, Cunningham A, Tsapogas P, Toellner KM, Brown G. Selective Expression of Flt3 within the Mouse Hematopoietic Stem Cell Compartment. Int J Mol Sci. 2017 May 12;18(5):1037. doi: 10.3390/ijms18051037. PMID 28498310; PMCID: PMC5454949.
  9. ^ Huret J-L. "FLT3 (FMS-like tyrosine kinase 3)". Atlas of Genetics and Cytogenetics in Oncology and Haematology. University Hospital of Poitiers.
  10. ^ Chew S, Mackey MC, Jabbour E (2020). "Gilteritinib in the treatment of relapsed and refractory acute myeloid leukemia with a FLT3 mutation". Review. Therapeutic Advances in Hematology. 11: 2040620720930614. doi:10.1177/2040620720930614. PMC 7271272. PMID 32547718.
  11. ^ Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. (October 2019). "FLT3-Mutated AML". The New England Journal of Medicine. 381 (18): 1728–1740. doi:10.1056/NEJMoa1902688. PMID 31665578.
  12. ^ "Gilteritinib Granted Orphan Drug Status for Acute Myeloid Leukemia". 20 July 2017.
  13. ^ "FDA approves gilteritinib for relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutatation". Drugs. FDA. December 14, 2018. Retrieved July 21, 2023.
  14. ^ a b "FDA approves quizartinib for newly diagnosed acute myeloid leukemia". Drugs. FDA. July 20, 2023. Retrieved July 21, 2023.
  15. ^ Office of the Commissioner. "Press Announcements - FDA approves new combination treatment for acute myeloid leukemia". www.fda.gov. Retrieved 2017-05-04.
  16. ^ Metzelder S, Wang Y, Wollmer E, Wanzel M, Teichler S, Chaturvedi A, Eilers M, Enghofer E, Neubauer A, Burchert A (June 2009). "Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation". Blood. 113 (26): 6567–71. doi:10.1182/blood-2009-03-208298. PMID 19389879. S2CID 206878993.
  17. ^ Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X, Estrov Z, Quintás-Cardama A, Small D, Cortes J, Andreeff M (February 2008). "Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia". J. Natl. Cancer Inst. 100 (3): 184–98. doi:10.1093/jnci/djm328. PMID 18230792.
  18. ^ Smith CC, Wang Q, Chin CS, Salerno S, Damon LE, Levis MJ, et al. (April 2012). "Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia". Nature. 485 (7397): 260–3. Bibcode:2012Natur.485..260S. doi:10.1038/nature11016. PMC 3390926. PMID 22504184.

Further reading edit

  • Kazi JU, Rönnstrand L (2019). "FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications". Physiol Rev. 99 (3): 1433–1466. doi:10.1152/physrev.00029.2018. PMID 31066629.
  • Reilly JT (2003). "FLT3 and its role in the pathogenesis of acute myeloid leukaemia". Leuk. Lymphoma. 44 (1): 1–7. doi:10.1080/1042819021000040233. PMID 12691136. S2CID 28533250.
  • Kottaridis PD, Gale RE, Linch DC (2003). "Prognostic implications of the presence of FLT3 mutations in patients with acute myeloid leukemia". Leuk. Lymphoma. 44 (6): 905–13. doi:10.1080/1042819031000067503. PMID 12854887. S2CID 44447515.
  • Gilliland DG (2004). "FLT3-activating mutations in acute promyelocytic leukaemia: a rationale for risk-adapted therapy with FLT3 inhibitors". Best Practice & Research. Clinical Haematology. 16 (3): 409–17. doi:10.1016/S1521-6926(03)00063-X. PMID 12935959.
  • Drexler HG, Quentmeier H (2005). "FLT3: receptor and ligand". Growth Factors. 22 (2): 71–3. doi:10.1080/08977190410001700989. PMID 15253381. S2CID 86614476.
  • Naoe T, Kiyoi H (2005). "Normal and oncogenic FLT3". Cell. Mol. Life Sci. 61 (23): 2932–8. doi:10.1007/s00018-004-4274-x. PMID 15583855. S2CID 27189321.
  • Sternberg DW, Licht JD (2005). "Therapeutic intervention in leukemias that express the activated fms-like tyrosine kinase 3 (FLT3): opportunities and challenges". Curr. Opin. Hematol. 12 (1): 7–13. doi:10.1097/01.moh.0000147891.06584.d7. PMID 15604885. S2CID 1590938.
  • Marcucci G, Mrózek K, Bloomfield CD (2005). "Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics". Curr. Opin. Hematol. 12 (1): 68–75. doi:10.1097/01.moh.0000149608.29685.d1. PMID 15604894. S2CID 6183391.
  • Markovic A, MacKenzie KL, Lock RB (2005). "FLT-3: a new focus in the understanding of acute leukemia". Int. J. Biochem. Cell Biol. 37 (6): 1168–72. doi:10.1016/j.biocel.2004.12.005. PMID 15778081.
  • Zheng R, Small D (2006). "Mutant FLT3 signaling contributes to a block in myeloid differentiation". Leuk. Lymphoma. 46 (12): 1679–87. doi:10.1080/10428190500261740. PMID 16263569. S2CID 20518363.
  • Parcells BW, Ikeda AK, Simms-Waldrip T, et al. (2007). "FMS-like tyrosine kinase 3 in normal hematopoiesis and acute myeloid leukemia". Stem Cells. 24 (5): 1174–84. doi:10.1634/stemcells.2005-0519. PMID 16410383.
  • Stubbs MC, Armstrong SA (2007). "FLT3 as a therapeutic target in childhood acute leukemia". Current Drug Targets. 8 (6): 703–14. doi:10.2174/138945007780830782. PMID 17584026.

External links edit

  • CD135+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • Human FLT3 genome location and FLT3 gene details page in the UCSC Genome Browser.
  • Overview of all the structural information available in the PDB for UniProt: P36888 (Receptor-type tyrosine-protein kinase FLT3) at the PDBe-KB.

January 01, 1970
cd135, cluster, differentiation, antigen, also, known, like, tyrosine, kinase, with, standing, feline, mcdonough, sarcoma, receptor, type, tyrosine, protein, kinase, flt3, fetal, liver, kinase, flk2, protein, that, humans, encoded, flt3, gene, flt3, cytokine, . Cluster of differentiation antigen 135 CD135 also known as fms like tyrosine kinase 3 FLT 3 with fms standing for feline McDonough sarcoma receptor type tyrosine protein kinase FLT3 or fetal liver kinase 2 Flk2 is a protein that in humans is encoded by the FLT3 gene FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III CD135 is the receptor for the cytokine Flt3 ligand FLT3L FLT3Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1RJB 3QS7 3QS9 4RT7 4XUFIdentifiersAliasesFLT3 CD135 FLK 2 FLK2 STK1 fms related tyrosine kinase 3 fms related receptor tyrosine kinase 3External IDsOMIM 136351 MGI 95559 HomoloGene 3040 GeneCards FLT3Gene location Human Chr Chromosome 13 human 1 Band13q12 2Start28 003 274 bp 1 End28 100 592 bp 1 Gene location Mouse Chr Chromosome 5 mouse 2 Band5 86 88 cM 5 G3Start147 267 551 bp 2 End147 337 299 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incerebellar hemispheremonocytebone marrow cellslymph nodebody of pancreasspleenappendixgallbladderright lungbloodTop expressed insuperior olivary complexfacial motor nucleusred nucleuscochlear nucleimotor neuronRegion IV of hippocampus properPurkinje cellanterior horn of spinal cordnerveinferior colliculusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionvascular endothelial growth factor activated receptor activity nucleotide binding protein kinase activity transferase activity protein homodimerization activity kinase activity protein binding cytokine receptor activity transmembrane receptor protein tyrosine kinase activity protein tyrosine kinase activity ATP binding protein self association protein containing complex binding glucocorticoid receptor binding 1 phosphatidylinositol 3 kinase activity receptor tyrosine kinase transmembrane signaling receptor activityCellular componentcytoplasm integral component of membrane cytosol endoplasmic reticulum lumen membrane integral component of plasma membrane nucleus plasma membrane endoplasmic reticulum protein containing complex receptor complexBiological processleukocyte homeostasis regulation of apoptotic process dendritic cell differentiation cell differentiation myeloid progenitor cell differentiation positive regulation of MAP kinase activity phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway common myeloid progenitor cell proliferation positive regulation of tyrosine phosphorylation of STAT protein cellular response to cytokine stimulus positive regulation of phosphatidylinositol 3 kinase activity protein phosphorylation pro B cell differentiation cellular response to glucocorticoid stimulus animal organ regeneration response to organonitrogen compound positive regulation of cell population proliferation lymphocyte proliferation protein autophosphorylation positive regulation of phosphatidylinositol 3 kinase signaling peptidyl tyrosine phosphorylation B cell differentiation positive regulation of MAPK cascade vascular endothelial growth factor signaling pathway cytokine mediated signaling pathway hemopoiesis MAPK cascade phosphatidylinositol 3 phosphate biosynthetic process negative regulation of signal transduction viral process negative regulation of apoptotic process positive regulation of ERK1 and ERK2 cascade hematopoietic progenitor cell differentiation leukocyte differentiation lymphocyte differentiationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez232214255EnsemblENSG00000122025ENSMUSG00000042817UniProtP36888Q00342RefSeq mRNA NM 004119NM 010229RefSeq protein NP 004110NP 034359Location UCSC Chr 13 28 28 1 MbChr 5 147 27 147 34 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse It is expressed on the surface of many hematopoietic progenitor cells Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells The FLT3 gene is one of the most frequently mutated genes in acute myeloid leukemia AML 5 High levels of wild type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations These high levels may be associated with worse prognosis Contents 1 Structure 2 Function 3 Clinical significance 3 1 Cell surface marker 3 2 Role in cancer 3 3 FLT3 inhibitors 4 See also 5 References 6 Further reading 7 External linksStructure editFLT3 is composed of five extracellular immunoglobulin like domains an extracellular domain a transmembrane domain a juxtamembrane domain and a tyrosine kinase domain consisting of 2 lobes that are connected by a tyrosine kinase insert Cytoplasmic FLT3 undergoes glycosylation which promotes localization of the receptor to the membrane 6 Function editCD135 is a class III receptor tyrosine kinase When this receptor binds to FLT3L a ternary complex is formed in which two FLT3 molecules are bridged by one homodimeric FLT3L 7 The formation of such complex brings the two intracellular domains in close proximity to each other eliciting initial trans phosphorylation of each kinase domain This initial phosphorylation event further activates the intrinsic tyrosine kinase activity which in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell Signaling through CD135 plays a role in cell survival proliferation and differentiation CD135 is important for lymphocyte B cell and T cell development Two cytokines that down modulate FLT3 activity amp block FLT3 induced hematopoietic activity are TNF alpha Tumor necrosis factor alpha TGF beta Transforming growth factor beta TGF beta especially decreases FLT3 protein levels and reverses the FLT3L induced decrease in the time that hematopoietic progenitors spend in the G1 phase of the cell cycle 6 Clinical significance editCell surface marker edit Cluster of differentiation CD molecules are markers on the cell surface as recognized by specific sets of antibodies used to identify the cell type stage of differentiation and activity of a cell In mice CD135 is expressed on several hematopoietic blood cells including long and short term reconstituting hematopoietic stem cells HSC and other progenitors like multipotent progenitors MPPs and common lymphoid progenitors CLP 8 Role in cancer edit CD135 is a proto oncogene meaning that mutations of this protein can lead to cancer 9 Mutations of the FLT3 receptor can lead to the development of leukemia a cancer of bone marrow hematopoietic progenitors Internal tandem duplications of FLT3 FLT3 ITD are the most common mutations associated with acute myelogenous leukemia AML and are a prognostic indicator associated with adverse disease outcome FLT3 inhibitors edit Gilteritinib a dual FLT3 AXL tyrosine kinase inhibitor 10 has completed a phase 3 trial of relapsed refractory acute myeloid leukemia in patients with FLT3 ITD or TKD mutations 11 In 2017 gilteritinib gained FDA orphan drug status for AML 12 In November 2018 the FDA approved gilteritinib Xospata for treatment of adult patients with relapsed or refractory acute myeloid leukemia AML with a FLT3 mutation as detected by an FDA approved test 13 In July 2023 quizartinib Vanflyta was also approved for the treatment of newly diagnosed AML with FLT3 internal tandem duplication ITD positive as detected by an FDA approved test 14 Precisely it should be used with standard cytarabine and anthracycline induction and cytarabine consolidation and as maintenance monotherapy following consolidation chemotherapy 14 Midostaurin was approved by the FDA in April 2017 for the treatment of adult patients with newly diagnosed AML who are positive for oncogenic FLT3 in combination with chemotherapy 15 The drug is approved for use with a companion diagnostic the LeukoStrat CDx FLT3 Mutation Assay which is used to detect the FLT3 mutation in patients with AML Sorafenib has been reported to show significant activity against Flt3 ITD positive acute myelogenous leukemia 16 17 Sunitinib also inhibits Flt3 Lestaurtinib is in clinical trials A paper published in Nature in April 2012 studied patients who developed resistance to FLT3 inhibitors finding specific DNA sites contributing to that resistance and highlighting opportunities for future development of inhibitors that could take into account the resistance conferring mutations for a more potent treatment 18 See also editCluster of differentiation cytokine receptor receptor tyrosine kinase tyrosine kinase oncogene hematopoiesis Lymphopoiesis Labeling lymphopoiesisReferences edit a b c GRCh38 Ensembl release 89 ENSG00000122025 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000042817 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Yamamoto Y Kiyoi H Nakano Y Suzuki R Kodera Y Miyawaki S Asou N Kuriyama K Yagasaki F Shimazaki C Akiyama H Saito K Nishimura M Motoji T Shinagawa K Takeshita A Saito H Ueda R Ohno R Naoe T April 2001 Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies Blood 97 8 2434 9 doi 10 1182 blood V97 8 2434 PMID 11290608 a b FLT3 Signaling Pathway Central SABiosciences Archived from the original on 2017 11 11 Retrieved 2012 12 18 Verstraete K Vandriessche G Januar M Elegheert J Shkumatov AV Desfosses A Van Craenenbroeck K Svergun DI Gutsche I Vergauwen B Savvides SN February 2011 Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex Blood 118 1 60 68 doi 10 1182 blood 2011 01 329532 PMID 21389326 Mooney CJ Cunningham A Tsapogas P Toellner KM Brown G Selective Expression of Flt3 within the Mouse Hematopoietic Stem Cell Compartment Int J Mol Sci 2017 May 12 18 5 1037 doi 10 3390 ijms18051037 PMID 28498310 PMCID PMC5454949 Huret J L FLT3 FMS like tyrosine kinase 3 Atlas of Genetics and Cytogenetics in Oncology and Haematology University Hospital of Poitiers Chew S Mackey MC Jabbour E 2020 Gilteritinib in the treatment of relapsed and refractory acute myeloid leukemia with a FLT3 mutation Review Therapeutic Advances in Hematology 11 2040620720930614 doi 10 1177 2040620720930614 PMC 7271272 PMID 32547718 Perl AE Martinelli G Cortes JE Neubauer A Berman E Paolini S et al October 2019 FLT3 Mutated AML The New England Journal of Medicine 381 18 1728 1740 doi 10 1056 NEJMoa1902688 PMID 31665578 Gilteritinib Granted Orphan Drug Status for Acute Myeloid Leukemia 20 July 2017 FDA approves gilteritinib for relapsed or refractory acute myeloid leukemia AML with a FLT3 mutatation Drugs FDA December 14 2018 Retrieved July 21 2023 a b FDA approves quizartinib for newly diagnosed acute myeloid leukemia Drugs FDA July 20 2023 Retrieved July 21 2023 Office of the Commissioner Press Announcements FDA approves new combination treatment for acute myeloid leukemia www fda gov Retrieved 2017 05 04 Metzelder S Wang Y Wollmer E Wanzel M Teichler S Chaturvedi A Eilers M Enghofer E Neubauer A Burchert A June 2009 Compassionate use of sorafenib in FLT3 ITD positive acute myeloid leukemia sustained regression before and after allogeneic stem cell transplantation Blood 113 26 6567 71 doi 10 1182 blood 2009 03 208298 PMID 19389879 S2CID 206878993 Zhang W Konopleva M Shi YX McQueen T Harris D Ling X Estrov Z Quintas Cardama A Small D Cortes J Andreeff M February 2008 Mutant FLT3 a direct target of sorafenib in acute myelogenous leukemia J Natl Cancer Inst 100 3 184 98 doi 10 1093 jnci djm328 PMID 18230792 Smith CC Wang Q Chin CS Salerno S Damon LE Levis MJ et al April 2012 Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia Nature 485 7397 260 3 Bibcode 2012Natur 485 260S doi 10 1038 nature11016 PMC 3390926 PMID 22504184 Further reading editKazi JU Ronnstrand L 2019 FMS like Tyrosine Kinase 3 FLT3 From Basic Science to Clinical Implications Physiol Rev 99 3 1433 1466 doi 10 1152 physrev 00029 2018 PMID 31066629 Reilly JT 2003 FLT3 and its role in the pathogenesis of acute myeloid leukaemia Leuk Lymphoma 44 1 1 7 doi 10 1080 1042819021000040233 PMID 12691136 S2CID 28533250 Kottaridis PD Gale RE Linch DC 2003 Prognostic implications of the presence of FLT3 mutations in patients with acute myeloid leukemia Leuk Lymphoma 44 6 905 13 doi 10 1080 1042819031000067503 PMID 12854887 S2CID 44447515 Gilliland DG 2004 FLT3 activating mutations in acute promyelocytic leukaemia a rationale for risk adapted therapy with FLT3 inhibitors Best Practice amp Research Clinical Haematology 16 3 409 17 doi 10 1016 S1521 6926 03 00063 X PMID 12935959 Drexler HG Quentmeier H 2005 FLT3 receptor and ligand Growth Factors 22 2 71 3 doi 10 1080 08977190410001700989 PMID 15253381 S2CID 86614476 Naoe T Kiyoi H 2005 Normal and oncogenic FLT3 Cell Mol Life Sci 61 23 2932 8 doi 10 1007 s00018 004 4274 x PMID 15583855 S2CID 27189321 Sternberg DW Licht JD 2005 Therapeutic intervention in leukemias that express the activated fms like tyrosine kinase 3 FLT3 opportunities and challenges Curr Opin Hematol 12 1 7 13 doi 10 1097 01 moh 0000147891 06584 d7 PMID 15604885 S2CID 1590938 Marcucci G Mrozek K Bloomfield CD 2005 Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics Curr Opin Hematol 12 1 68 75 doi 10 1097 01 moh 0000149608 29685 d1 PMID 15604894 S2CID 6183391 Markovic A MacKenzie KL Lock RB 2005 FLT 3 a new focus in the understanding of acute leukemia Int J Biochem Cell Biol 37 6 1168 72 doi 10 1016 j biocel 2004 12 005 PMID 15778081 Zheng R Small D 2006 Mutant FLT3 signaling contributes to a block in myeloid differentiation Leuk Lymphoma 46 12 1679 87 doi 10 1080 10428190500261740 PMID 16263569 S2CID 20518363 Parcells BW Ikeda AK Simms Waldrip T et al 2007 FMS like tyrosine kinase 3 in normal hematopoiesis and acute myeloid leukemia Stem Cells 24 5 1174 84 doi 10 1634 stemcells 2005 0519 PMID 16410383 Stubbs MC Armstrong SA 2007 FLT3 as a therapeutic target in childhood acute leukemia Current Drug Targets 8 6 703 14 doi 10 2174 138945007780830782 PMID 17584026 External links editCD135 Antigen at the U S National Library of Medicine Medical Subject Headings MeSH Human FLT3 genome location and FLT3 gene details page in the UCSC Genome Browser Overview of all the structural information available in the PDB for UniProt P36888 Receptor type tyrosine protein kinase FLT3 at the PDBe KB Portal nbsp Biology Retrieved from https en wikipedia org w index php title CD135 amp oldid 1189998975, wikipedia, wiki, book, books, library,

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