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FLT3 NP_004110.2:p.M664I

MedGen UID:
1720277
•Concept ID:
C5238332
•
Cell or Molecular Dysfunction
Synonyms: CD135 Antigen M664I; CD135 Antigen Met664Ile; Fetal Liver Kinase-2 M664I; Fetal Liver Kinase-2 Met664Ile; Flt-3 Receptor M664I; Flt-3 Receptor Met664Ile; FLT3 M664I; FLT3 Met664Ile; FLT3 NP_004110.2:p.Met664Ile; FLT3 p.M664I; FLT3 p.Met664Ile; Fms-Related Tyrosine Kinase 3 M664I; Fms-Related Tyrosine Kinase 3 Met664Ile; M664I; NP_004110.2:p.M664I; NP_004110.2:p.Met664Ile; Receptor-Type Tyrosine-Protein Kinase FLT3 M664I; Receptor-Type Tyrosine-Protein Kinase FLT3 Met664Ile; Stem Cell Tyrosine Kinase 1 M664I; Stem Cell Tyrosine Kinase 1 Met664Ile

Definition

A change in the amino acid residue at position 664 in the receptor-type tyrosine-protein kinase FLT3 protein where methionine has been replaced by isoleucine. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFLT3 NP_004110.2:p.M664I

Professional guidelines

PubMed

FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML.
Othman J, Potter N, Mokretar K, Taussig D, Khan A, Krishnamurthy P, Latif AL, Cahalin P, Aries J, Amer M, Belsham E, Conneally E, Craddock C, Culligan D, Dennis M, Duncan C, Freeman SD, Furness C, Gilkes A, Gkreka P, Hodgson K, Ingram W, Jain M, King A, Knapper S, Kottaridis P, McMullin MF, Mohite U, Ngu L, O'Nions J, Patrick K, Rider T, Roberts W, Severinsen MT, Storrar N, Taylor T, Russell NH, Dillon R
Leukemia 2023 Oct;37(10):2066-2072. Epub 2023 Aug 9 doi: 10.1038/s41375-023-01994-x. PMID: 37558736Free PMC Article

Recent clinical studies

Etiology

Prognostic risk signature in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax.
Bataller A, Bazinet A, DiNardo CD, Maiti A, Borthakur G, Daver NG, Short NJ, Jabbour EJ, Issa GC, Pemmaraju N, Yilmaz M, Montalban-Bravo G, Takahashi K, Loghavi S, Garcia-Manero G, Ravandi F, Kantarjian HM, Kadia TM
Blood Adv 2024 Feb 27;8(4):927-935. doi: 10.1182/bloodadvances.2023011757. PMID: 38113472Free PMC Article
FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML.
Othman J, Potter N, Mokretar K, Taussig D, Khan A, Krishnamurthy P, Latif AL, Cahalin P, Aries J, Amer M, Belsham E, Conneally E, Craddock C, Culligan D, Dennis M, Duncan C, Freeman SD, Furness C, Gilkes A, Gkreka P, Hodgson K, Ingram W, Jain M, King A, Knapper S, Kottaridis P, McMullin MF, Mohite U, Ngu L, O'Nions J, Patrick K, Rider T, Roberts W, Severinsen MT, Storrar N, Taylor T, Russell NH, Dillon R
Leukemia 2023 Oct;37(10):2066-2072. Epub 2023 Aug 9 doi: 10.1038/s41375-023-01994-x. PMID: 37558736Free PMC Article
Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.
Kadia TM, Reville PK, Borthakur G, Yilmaz M, Kornblau S, Alvarado Y, Dinardo CD, Daver N, Jain N, Pemmaraju N, Short N, Wang SA, Tidwell RSS, Islam R, Konopleva M, Garcia-Manero G, Ravandi F, Kantarjian HM
Lancet Haematol 2021 Aug;8(8):e552-e561. doi: 10.1016/S2352-3026(21)00192-7. PMID: 34329576Free PMC Article
Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML.
Yilmaz M, Alfayez M, DiNardo CD, Borthakur G, Kadia TM, Konopleva MY, Loghavi S, Kanagal-Shamanna R, Patel KP, Jabbour EJ, Garcia-Manero G, Pemmaraju N, Pierce SA, Ghayas I, Short NJ, Montalban-Bravo G, Takahashi K, Assi R, Alotaibi AS, Ohanian M, Andreeff M, Cortes JE, Kantarjian HM, Ravandi F, Daver NG
J Hematol Oncol 2020 Oct 8;13(1):132. doi: 10.1186/s13045-020-00964-5. PMID: 33032648Free PMC Article
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.
Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ
N Engl J Med 2019 Oct 31;381(18):1728-1740. doi: 10.1056/NEJMoa1902688. PMID: 31665578

Diagnosis

FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML.
Othman J, Potter N, Mokretar K, Taussig D, Khan A, Krishnamurthy P, Latif AL, Cahalin P, Aries J, Amer M, Belsham E, Conneally E, Craddock C, Culligan D, Dennis M, Duncan C, Freeman SD, Furness C, Gilkes A, Gkreka P, Hodgson K, Ingram W, Jain M, King A, Knapper S, Kottaridis P, McMullin MF, Mohite U, Ngu L, O'Nions J, Patrick K, Rider T, Roberts W, Severinsen MT, Storrar N, Taylor T, Russell NH, Dillon R
Leukemia 2023 Oct;37(10):2066-2072. Epub 2023 Aug 9 doi: 10.1038/s41375-023-01994-x. PMID: 37558736Free PMC Article
Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy.
Wang ES, Montesinos P, Minden MD, Lee JH, Heuser M, Naoe T, Chou WC, Laribi K, Esteve J, Altman JK, Havelange V, Watson AM, Gambacorti-Passerini C, Patkowska E, Liu S, Wu R, Philipose N, Hill JE, Gill SC, Rich ES, Tiu RV
Blood 2022 Oct 27;140(17):1845-1857. doi: 10.1182/blood.2021014586. PMID: 35917453Free PMC Article
Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.
Kadia TM, Reville PK, Borthakur G, Yilmaz M, Kornblau S, Alvarado Y, Dinardo CD, Daver N, Jain N, Pemmaraju N, Short N, Wang SA, Tidwell RSS, Islam R, Konopleva M, Garcia-Manero G, Ravandi F, Kantarjian HM
Lancet Haematol 2021 Aug;8(8):e552-e561. doi: 10.1016/S2352-3026(21)00192-7. PMID: 34329576Free PMC Article
Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.
Smith CC, Viny AD, Massi E, Kandoth C, Socci ND, Rapaport F, Najm M, Medina-Martinez JS, Papaemmanuil E, Tarver TC, Hsu HH, Le MH, West B, Bollag G, Taylor BS, Levine RL, Shah NP
Clin Cancer Res 2021 Jul 15;27(14):4003-4011. Epub 2021 Jun 8 doi: 10.1158/1078-0432.CCR-20-3458. PMID: 34103301Free PMC Article
Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses.
Chavan R, Marfatia KA, An IC, Garber DA, Feinberg MB
J Virol 2006 Aug;80(15):7676-87. doi: 10.1128/JVI.02748-05. PMID: 16840346Free PMC Article

Therapy

FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML.
Othman J, Potter N, Mokretar K, Taussig D, Khan A, Krishnamurthy P, Latif AL, Cahalin P, Aries J, Amer M, Belsham E, Conneally E, Craddock C, Culligan D, Dennis M, Duncan C, Freeman SD, Furness C, Gilkes A, Gkreka P, Hodgson K, Ingram W, Jain M, King A, Knapper S, Kottaridis P, McMullin MF, Mohite U, Ngu L, O'Nions J, Patrick K, Rider T, Roberts W, Severinsen MT, Storrar N, Taylor T, Russell NH, Dillon R
Leukemia 2023 Oct;37(10):2066-2072. Epub 2023 Aug 9 doi: 10.1038/s41375-023-01994-x. PMID: 37558736Free PMC Article
Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy.
Wang ES, Montesinos P, Minden MD, Lee JH, Heuser M, Naoe T, Chou WC, Laribi K, Esteve J, Altman JK, Havelange V, Watson AM, Gambacorti-Passerini C, Patkowska E, Liu S, Wu R, Philipose N, Hill JE, Gill SC, Rich ES, Tiu RV
Blood 2022 Oct 27;140(17):1845-1857. doi: 10.1182/blood.2021014586. PMID: 35917453Free PMC Article
Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.
Kadia TM, Reville PK, Borthakur G, Yilmaz M, Kornblau S, Alvarado Y, Dinardo CD, Daver N, Jain N, Pemmaraju N, Short N, Wang SA, Tidwell RSS, Islam R, Konopleva M, Garcia-Manero G, Ravandi F, Kantarjian HM
Lancet Haematol 2021 Aug;8(8):e552-e561. doi: 10.1016/S2352-3026(21)00192-7. PMID: 34329576Free PMC Article
Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML.
Yilmaz M, Alfayez M, DiNardo CD, Borthakur G, Kadia TM, Konopleva MY, Loghavi S, Kanagal-Shamanna R, Patel KP, Jabbour EJ, Garcia-Manero G, Pemmaraju N, Pierce SA, Ghayas I, Short NJ, Montalban-Bravo G, Takahashi K, Assi R, Alotaibi AS, Ohanian M, Andreeff M, Cortes JE, Kantarjian HM, Ravandi F, Daver NG
J Hematol Oncol 2020 Oct 8;13(1):132. doi: 10.1186/s13045-020-00964-5. PMID: 33032648Free PMC Article
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.
Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ
N Engl J Med 2019 Oct 31;381(18):1728-1740. doi: 10.1056/NEJMoa1902688. PMID: 31665578

Prognosis

Prognostic risk signature in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax.
Bataller A, Bazinet A, DiNardo CD, Maiti A, Borthakur G, Daver NG, Short NJ, Jabbour EJ, Issa GC, Pemmaraju N, Yilmaz M, Montalban-Bravo G, Takahashi K, Loghavi S, Garcia-Manero G, Ravandi F, Kantarjian HM, Kadia TM
Blood Adv 2024 Feb 27;8(4):927-935. doi: 10.1182/bloodadvances.2023011757. PMID: 38113472Free PMC Article
Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.
Kadia TM, Reville PK, Borthakur G, Yilmaz M, Kornblau S, Alvarado Y, Dinardo CD, Daver N, Jain N, Pemmaraju N, Short N, Wang SA, Tidwell RSS, Islam R, Konopleva M, Garcia-Manero G, Ravandi F, Kantarjian HM
Lancet Haematol 2021 Aug;8(8):e552-e561. doi: 10.1016/S2352-3026(21)00192-7. PMID: 34329576Free PMC Article
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.
Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ
N Engl J Med 2019 Oct 31;381(18):1728-1740. doi: 10.1056/NEJMoa1902688. PMID: 31665578
Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses.
Chavan R, Marfatia KA, An IC, Garber DA, Feinberg MB
J Virol 2006 Aug;80(15):7676-87. doi: 10.1128/JVI.02748-05. PMID: 16840346Free PMC Article

Clinical prediction guides

Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.
Kadia TM, Reville PK, Borthakur G, Yilmaz M, Kornblau S, Alvarado Y, Dinardo CD, Daver N, Jain N, Pemmaraju N, Short N, Wang SA, Tidwell RSS, Islam R, Konopleva M, Garcia-Manero G, Ravandi F, Kantarjian HM
Lancet Haematol 2021 Aug;8(8):e552-e561. doi: 10.1016/S2352-3026(21)00192-7. PMID: 34329576Free PMC Article
TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination.
Toy R, Keenum MC, Pradhan P, Phang K, Chen P, Chukwu C, Nguyen LAH, Liu J, Jain S, Kozlowski G, Hosten J, Suthar MS, Roy K
J Control Release 2021 Feb 10;330:866-877. Epub 2020 Nov 5 doi: 10.1016/j.jconrel.2020.10.060. PMID: 33160004Free PMC Article
Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses.
Chavan R, Marfatia KA, An IC, Garber DA, Feinberg MB
J Virol 2006 Aug;80(15):7676-87. doi: 10.1128/JVI.02748-05. PMID: 16840346Free PMC Article

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