U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

FLT3 Internal Tandem Duplication

MedGen UID:
385038
•Concept ID:
C2348499
•
Cell or Molecular Dysfunction
Synonyms: Activating FLT3-ITD Gene Mutation; Activating FLT3-ITD Mutation; FLT3 ITD; FLT3-ITD; FLT3-ITD Activating Mutation; FLT3-ITD Mutation; FLT3/ITD Mutation

Definition

A genetic abnormality that arises from duplications of the juxtamembrane portion of the gene and results in constitutive activation of the FLT3 receptor tyrosine kinase protein in early hematopoietic progenitor cells. It is associated with acute myelogenous leukemia where it appears to correlate with a poor prognosis. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFLT3 Internal Tandem Duplication

Professional guidelines

PubMed

The Clinical Utility of FLT3 Mutation Testing in Acute Leukemia: A Canadian Consensus.
Bergeron J, Capo-Chichi JM, Tsui H, Mahe E, Berardi P, Minden MD, Brandwein JM, Schuh AC
Curr Oncol 2023 Dec 12;30(12):10410-10436. doi: 10.3390/curroncol30120759. PMID: 38132393Free PMC Article
Treatment of older adults with FLT3-mutated AML: Emerging paradigms and the role of frontline FLT3 inhibitors.
Short NJ, Nguyen D, Ravandi F
Blood Cancer J 2023 Sep 11;13(1):142. doi: 10.1038/s41408-023-00911-w. PMID: 37696819Free PMC Article
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.
DiNardo CD, Tiong IS, Quaglieri A, MacRaild S, Loghavi S, Brown FC, Thijssen R, Pomilio G, Ivey A, Salmon JM, Glytsou C, Fleming SA, Zhang Q, Ma H, Patel KP, Kornblau SM, Xu Z, Chua CC, Chen X, Blombery P, Flensburg C, Cummings N, Aifantis I, Kantarjian H, Huang DCS, Roberts AW, Majewski IJ, Konopleva M, Wei AH
Blood 2020 Mar 12;135(11):791-803. doi: 10.1182/blood.2019003988. PMID: 31932844Free PMC Article

Recent clinical studies

Etiology

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.
Dillon LW, Gui G, Ravindra N, Andrew G, Mukherjee D, Wong ZC, Huang Y, Gerhold J, Holman M, D'Angelo J, Miller J, Higgins J, Salk JJ, Auletta JJ, El Chaer F, Devine SM, Jimenez-Jimenez AM, De Lima MJG, Litzow MR, Kebriaei P, Saber W, Spellman SR, Zeger SL, Page KM, Hourigan CS
JAMA Oncol 2024 Aug 1;10(8):1104-1110. doi: 10.1001/jamaoncol.2024.0985. PMID: 38696205Free PMC Article
Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial.
Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group
Lancet 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25 doi: 10.1016/S0140-6736(23)00464-6. PMID: 37116523
DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.
Dillon LW, Gui G, Page KM, Ravindra N, Wong ZC, Andrew G, Mukherjee D, Zeger SL, El Chaer F, Spellman S, Howard A, Chen K, Auletta J, Devine SM, Jimenez Jimenez AM, De Lima MJG, Litzow MR, Kebriaei P, Saber W, Weisdorf DJ, Hourigan CS
JAMA 2023 Mar 7;329(9):745-755. doi: 10.1001/jama.2023.1363. PMID: 36881031Free PMC Article
Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia.
Grob T, Sanders MA, Vonk CM, Kavelaars FG, Rijken M, Hanekamp DW, Gradowska PL, Cloos J, Fløisand Y, van Marwijk Kooy M, Manz MG, Ossenkoppele GJ, Tick LW, Havelange V, Löwenberg B, Jongen-Lavrencic M, Valk PJM
J Clin Oncol 2023 Feb 1;41(4):756-765. Epub 2022 Oct 31 doi: 10.1200/JCO.22.00715. PMID: 36315929Free PMC Article
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN).
Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, Wollmer E, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner EM, Kröger N, Wolschke C, Schleuning M, Götze KS, Schmid C, Crysandt M, Eßeling E, Wolf D, Wang Y, Böhm A, Thiede C, Haferlach T, Michel C, Bethge W, Wündisch T, Brandts C, Harnisch S, Wittenberg M, Hoeffkes HG, Rospleszcz S, Burchardt A, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK
J Clin Oncol 2020 Sep 10;38(26):2993-3002. Epub 2020 Jul 16 doi: 10.1200/JCO.19.03345. PMID: 32673171

Diagnosis

Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory FLT3-Mutated AML.
Short NJ, Daver N, Dinardo CD, Kadia T, Nasr LF, Macaron W, Yilmaz M, Borthakur G, Montalban-Bravo G, Garcia-Manero G, Issa GC, Chien KS, Jabbour E, Nasnas C, Huang X, Qiao W, Matthews J, Stojanik CJ, Patel KP, Abramova R, Thankachan J, Konopleva M, Kantarjian H, Ravandi F
J Clin Oncol 2024 May 1;42(13):1499-1508. Epub 2024 Jan 26 doi: 10.1200/JCO.23.01911. PMID: 38277619Free PMC Article
Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial.
Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group
Lancet 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25 doi: 10.1016/S0140-6736(23)00464-6. PMID: 37116523
DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.
Dillon LW, Gui G, Page KM, Ravindra N, Wong ZC, Andrew G, Mukherjee D, Zeger SL, El Chaer F, Spellman S, Howard A, Chen K, Auletta J, Devine SM, Jimenez Jimenez AM, De Lima MJG, Litzow MR, Kebriaei P, Saber W, Weisdorf DJ, Hourigan CS
JAMA 2023 Mar 7;329(9):745-755. doi: 10.1001/jama.2023.1363. PMID: 36881031Free PMC Article
Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia.
Grob T, Sanders MA, Vonk CM, Kavelaars FG, Rijken M, Hanekamp DW, Gradowska PL, Cloos J, Fløisand Y, van Marwijk Kooy M, Manz MG, Ossenkoppele GJ, Tick LW, Havelange V, Löwenberg B, Jongen-Lavrencic M, Valk PJM
J Clin Oncol 2023 Feb 1;41(4):756-765. Epub 2022 Oct 31 doi: 10.1200/JCO.22.00715. PMID: 36315929Free PMC Article
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.
DiNardo CD, Tiong IS, Quaglieri A, MacRaild S, Loghavi S, Brown FC, Thijssen R, Pomilio G, Ivey A, Salmon JM, Glytsou C, Fleming SA, Zhang Q, Ma H, Patel KP, Kornblau SM, Xu Z, Chua CC, Chen X, Blombery P, Flensburg C, Cummings N, Aifantis I, Kantarjian H, Huang DCS, Roberts AW, Majewski IJ, Konopleva M, Wei AH
Blood 2020 Mar 12;135(11):791-803. doi: 10.1182/blood.2019003988. PMID: 31932844Free PMC Article

Therapy

Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory FLT3-Mutated AML.
Short NJ, Daver N, Dinardo CD, Kadia T, Nasr LF, Macaron W, Yilmaz M, Borthakur G, Montalban-Bravo G, Garcia-Manero G, Issa GC, Chien KS, Jabbour E, Nasnas C, Huang X, Qiao W, Matthews J, Stojanik CJ, Patel KP, Abramova R, Thankachan J, Konopleva M, Kantarjian H, Ravandi F
J Clin Oncol 2024 May 1;42(13):1499-1508. Epub 2024 Jan 26 doi: 10.1200/JCO.23.01911. PMID: 38277619Free PMC Article
Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial.
Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group
Lancet 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25 doi: 10.1016/S0140-6736(23)00464-6. PMID: 37116523
Outcomes in Patients with FLT3-Mutated Relapsed/ Refractory Acute Myelogenous Leukemia Who Underwent Transplantation in the Phase 3 ADMIRAL Trial of Gilteritinib versus Salvage Chemotherapy.
Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Recher C, Yoon SS, Maeda Y, Hosono N, Onozawa M, Kato T, Kim HJ, Hasabou N, Nuthethi R, Tiu R, Levis MJ
Transplant Cell Ther 2023 Apr;29(4):265.e1-265.e10. Epub 2022 Dec 13 doi: 10.1016/j.jtct.2022.12.006. PMID: 36526260Free PMC Article
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN).
Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, Wollmer E, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner EM, Kröger N, Wolschke C, Schleuning M, Götze KS, Schmid C, Crysandt M, Eßeling E, Wolf D, Wang Y, Böhm A, Thiede C, Haferlach T, Michel C, Bethge W, Wündisch T, Brandts C, Harnisch S, Wittenberg M, Hoeffkes HG, Rospleszcz S, Burchardt A, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK
J Clin Oncol 2020 Sep 10;38(26):2993-3002. Epub 2020 Jul 16 doi: 10.1200/JCO.19.03345. PMID: 32673171
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.
DiNardo CD, Tiong IS, Quaglieri A, MacRaild S, Loghavi S, Brown FC, Thijssen R, Pomilio G, Ivey A, Salmon JM, Glytsou C, Fleming SA, Zhang Q, Ma H, Patel KP, Kornblau SM, Xu Z, Chua CC, Chen X, Blombery P, Flensburg C, Cummings N, Aifantis I, Kantarjian H, Huang DCS, Roberts AW, Majewski IJ, Konopleva M, Wei AH
Blood 2020 Mar 12;135(11):791-803. doi: 10.1182/blood.2019003988. PMID: 31932844Free PMC Article

Prognosis

Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML.
Othman J, Potter N, Ivey A, Tazi Y, Papaemmanuil E, Jovanovic J, Freeman SD, Gilkes A, Gale R, Rapoz-D'Silva T, Runglall M, Kleeman M, Dhami P, Thomas I, Johnson S, Canham J, Cavenagh J, Kottaridis P, Arnold C, Ommen HB, Overgaard UM, Dennis M, Burnett A, Wilhelm-Benartzi C, Huntly B, Russell NH, Dillon R
Blood 2024 Aug 15;144(7):714-728. doi: 10.1182/blood.2024024310. PMID: 38691678
Treatment of older adults with FLT3-mutated AML: Emerging paradigms and the role of frontline FLT3 inhibitors.
Short NJ, Nguyen D, Ravandi F
Blood Cancer J 2023 Sep 11;13(1):142. doi: 10.1038/s41408-023-00911-w. PMID: 37696819Free PMC Article
Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia.
Grob T, Sanders MA, Vonk CM, Kavelaars FG, Rijken M, Hanekamp DW, Gradowska PL, Cloos J, Fløisand Y, van Marwijk Kooy M, Manz MG, Ossenkoppele GJ, Tick LW, Havelange V, Löwenberg B, Jongen-Lavrencic M, Valk PJM
J Clin Oncol 2023 Feb 1;41(4):756-765. Epub 2022 Oct 31 doi: 10.1200/JCO.22.00715. PMID: 36315929Free PMC Article
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN).
Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, Wollmer E, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner EM, Kröger N, Wolschke C, Schleuning M, Götze KS, Schmid C, Crysandt M, Eßeling E, Wolf D, Wang Y, Böhm A, Thiede C, Haferlach T, Michel C, Bethge W, Wündisch T, Brandts C, Harnisch S, Wittenberg M, Hoeffkes HG, Rospleszcz S, Burchardt A, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK
J Clin Oncol 2020 Sep 10;38(26):2993-3002. Epub 2020 Jul 16 doi: 10.1200/JCO.19.03345. PMID: 32673171
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.
DiNardo CD, Tiong IS, Quaglieri A, MacRaild S, Loghavi S, Brown FC, Thijssen R, Pomilio G, Ivey A, Salmon JM, Glytsou C, Fleming SA, Zhang Q, Ma H, Patel KP, Kornblau SM, Xu Z, Chua CC, Chen X, Blombery P, Flensburg C, Cummings N, Aifantis I, Kantarjian H, Huang DCS, Roberts AW, Majewski IJ, Konopleva M, Wei AH
Blood 2020 Mar 12;135(11):791-803. doi: 10.1182/blood.2019003988. PMID: 31932844Free PMC Article

Clinical prediction guides

Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML.
Othman J, Potter N, Ivey A, Tazi Y, Papaemmanuil E, Jovanovic J, Freeman SD, Gilkes A, Gale R, Rapoz-D'Silva T, Runglall M, Kleeman M, Dhami P, Thomas I, Johnson S, Canham J, Cavenagh J, Kottaridis P, Arnold C, Ommen HB, Overgaard UM, Dennis M, Burnett A, Wilhelm-Benartzi C, Huntly B, Russell NH, Dillon R
Blood 2024 Aug 15;144(7):714-728. doi: 10.1182/blood.2024024310. PMID: 38691678
Treatment of older adults with FLT3-mutated AML: Emerging paradigms and the role of frontline FLT3 inhibitors.
Short NJ, Nguyen D, Ravandi F
Blood Cancer J 2023 Sep 11;13(1):142. doi: 10.1038/s41408-023-00911-w. PMID: 37696819Free PMC Article
DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.
Dillon LW, Gui G, Page KM, Ravindra N, Wong ZC, Andrew G, Mukherjee D, Zeger SL, El Chaer F, Spellman S, Howard A, Chen K, Auletta J, Devine SM, Jimenez Jimenez AM, De Lima MJG, Litzow MR, Kebriaei P, Saber W, Weisdorf DJ, Hourigan CS
JAMA 2023 Mar 7;329(9):745-755. doi: 10.1001/jama.2023.1363. PMID: 36881031Free PMC Article
Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications.
Döhner H, Weber D, Krzykalla J, Fiedler W, Wulf G, Salih H, Lübbert M, Kühn MWM, Schroeder T, Salwender H, Götze K, Westermann J, Fransecky L, Mayer K, Hertenstein B, Ringhoffer M, Tischler HJ, Machherndl-Spandl S, Schrade A, Paschka P, Gaidzik VI, Theis F, Thol F, Heuser M, Schlenk RF, Bullinger L, Saadati M, Benner A, Larson R, Stone R, Döhner K, Ganser A
Blood Adv 2022 Sep 27;6(18):5345-5355. doi: 10.1182/bloodadvances.2022007223. PMID: 35486475Free PMC Article
Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies.
Michmerhuizen NL, Klco JM, Mullighan CG
Blood 2020 Nov 12;136(20):2275-2289. doi: 10.1182/blood.2020007093. PMID: 32766874Free PMC Article

Recent systematic reviews

Association of FLT3-internal tandem duplication length with overall survival in acute myeloid leukemia: a systematic review and meta-analysis.
Polak TB, Van Rosmalen J, Dirven S, Herzig JK, Cloos J, Meshinchi S, Döhner K, Janssen JJWM, Cucchi DGJ
Haematologica 2022 Oct 1;107(10):2506-2510. doi: 10.3324/haematol.2022.281218. PMID: 35796012Free PMC Article
TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.
Gagelmann N, Wolschke C, Klyuchnikov E, Christopeit M, Ayuk F, Kröger N
Front Immunol 2021;12:630429. Epub 2021 Mar 12 doi: 10.3389/fimmu.2021.630429. PMID: 33790903Free PMC Article
Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis.
Port M, Böttcher M, Thol F, Ganser A, Schlenk R, Wasem J, Neumann A, Pouryamout L
Ann Hematol 2014 Aug;93(8):1279-86. Epub 2014 May 7 doi: 10.1007/s00277-014-2072-6. PMID: 24801015
Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations in acute promyelocytic leukemia: a systematic review.
Beitinjaneh A, Jang S, Roukoz H, Majhail NS
Leuk Res 2010 Jul;34(7):831-6. Epub 2010 Jan 21 doi: 10.1016/j.leukres.2010.01.001. PMID: 20096459

Supplemental Content

Table of contents

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...