{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:25:43Z","timestamp":1790040343246,"version":"4.0.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,22]]},"DOI":"10.7759\/cureus.45765","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T11:22:23Z","timestamp":1695381743000},"source":"Crossref","is-referenced-by-count":13,"title":["FLT3 Mutations in Acute Myeloid Leukemia: Unraveling the Molecular Mechanisms and Implications for Targeted Therapies"],"prefix":"10.7759","author":[{"given":"Meryem","family":"Jalte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriame","family":"Abbassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinde","family":"El Mouhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanae","family":"Daha Belghiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ahakoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hicham","family":"Bekkari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406184","article-title":"Acute myeloid leukemia","volume":"373","author":"D\u00f6hner H","year":"2015","unstructured":"D\u00f6hner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015, 373:1136-52. 10.1056\/NEJMra1406184","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100905","article-title":"A review of FLT3 inhibitors in acute myeloid leukemia","volume":"52","author":"Zhao JC","year":"2022","unstructured":"Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Rev. 2022, 52:100905. 10.1016\/j.blre.2021.100905","journal-title":"Blood Rev"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.3762","article-title":"IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication","volume":"28","author":"Paschka P","year":"2010","unstructured":"Paschka P, Schlenk RF, Gaidzik VI, et al.. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol. 2010, 28:3636-43. 10.1200\/JCO.2010.28.3762","journal-title":"J Clin Oncol"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2013.1.220","article-title":"FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?","volume":"2013","author":"Levis M","year":"2013","unstructured":"Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?. Hematol Am Soc Hematol Educ Program. 2013, 2013:220-6. 10.1182\/asheducation-2013.1.220","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2021.22.10.3245","article-title":"Frequency of FLT3 internal tandem duplications in adult Syrian patients with acute myeloid leukemia and normal karyotype","volume":"22","author":"Al-Arbeed IF","year":"2021","unstructured":"Al-Arbeed IF, Wafa A, Moassass F, Al-Halabi B, Al-Achkar W, Abou-Khamis I. Frequency of FLT3 internal tandem duplications in adult Syrian patients with acute myeloid leukemia and normal karyotype. Asian Pac J Cancer Prev. 2021, 22:3245-51. 10.31557\/APJCP.2021.22.10.3245","journal-title":"Asian Pac J Cancer Prev"},{"key":"ref6","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"D\u00f6hner H","year":"2017","unstructured":"D\u00f6hner H, Estey E, Grimwade D, et al.. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017, 129:424-47.","journal-title":"Blood"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007626","article-title":"Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin","volume":"137","author":"Schmalbrock LK","year":"2021","unstructured":"Schmalbrock LK, Dolnik A, Cocciardi S, et al.. Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin. Blood. 2021, 137:3093-104. 10.1182\/blood.2020007626","journal-title":"Blood"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104725","article-title":"The role of small molecule Flt3 receptor protein-tyrosine kinase inhibitors in the treatment of Flt3-positive acute myelogenous leukemias","volume":"155","author":"Roskoski R Jr","year":"2020","unstructured":"Roskoski R Jr. The role of small molecule Flt3 receptor protein-tyrosine kinase inhibitors in the treatment of Flt3-positive acute myelogenous leukemias. Pharmacol Res. 2020, 155:104725. 10.1016\/j.phrs.2020.104725","journal-title":"Pharmacol Res"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-020-02587-3","article-title":"De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report","volume":"15","author":"Alarbeed IF","year":"2021","unstructured":"Alarbeed IF, Wafa A, Moassass F, Al-Halabi B, Al-Achkar W, Liehr T, Aboukhamis I. De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report. J Med Case Rep. 2021, 15:22. 10.1186\/s13256-020-02587-3","journal-title":"J Med Case Rep"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2014.00263","article-title":"The biology and targeting of FLT3 in pediatric leukemia","volume":"4","author":"Annesley CE","year":"2014","unstructured":"Annesley CE, Brown P. The biology and targeting of FLT3 in pediatric leukemia. Front Oncol. 2014, 4:263. 10.3389\/fonc.2014.00263","journal-title":"Front Oncol"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.9678","article-title":"Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3","volume":"28","author":"Fischer T","year":"2010","unstructured":"Fischer T, Stone RM, Deangelo DJ, et al.. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010, 28:4339-45. 10.1200\/JCO.2010.28.9678","journal-title":"J Clin Oncol"},{"key":"ref12","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V95.11.3489","article-title":"Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells","volume":"95","author":"McKenna HJ","year":"2000","unstructured":"McKenna HJ, Stocking KL, Miller RE, et al.. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood. 2000, 95:3489-97.","journal-title":"Blood"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403220","article-title":"Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias","volume":"18","author":"Zhao S","year":"2004","unstructured":"Zhao S, Konopleva M, Cabreira-Hansen M, et al.. Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias. Leukemia. 2004, 18:267-75. 10.1038\/sj.leu.2403220","journal-title":"Leukemia"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq120","article-title":"Activation of Akt and MAPK pathways enhances the tumorigenicity of CD133+ primary colon cancer cells","volume":"31","author":"Wang YK","year":"2010","unstructured":"Wang YK, Zhu YL, Qiu FM, Zhang T, Chen ZG, Zheng S, Huang J. Activation of Akt and MAPK pathways enhances the tumorigenicity of CD133+ primary colon cancer cells. Carcinogenesis. 2010, 31:1376-80. 10.1093\/carcin\/bgq120","journal-title":"Carcinogenesis"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403099","article-title":"FLT3: ITDoes matter in leukemia","volume":"17","author":"Levis M","year":"2003","unstructured":"Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia. 2003, 17:1738-52. 10.1038\/sj.leu.2403099","journal-title":"Leukemia"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400756","article-title":"Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho)","volume":"11","author":"Kiyoi H","year":"1997","unstructured":"Kiyoi H, Naoe T, Yokota S, et al.. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia. 1997, 11:1447-52. 10.1038\/sj.leu.2400756","journal-title":"Leukemia"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa074306","article-title":"Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia","volume":"358","author":"Schlenk RF","year":"2008","unstructured":"Schlenk RF, D\u00f6hner K, Krauter J, et al.. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008, 358:1909-18. 10.1056\/NEJMoa074306","journal-title":"N Engl J Med"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-107946","article-title":"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","volume":"111","author":"Whitman SP","year":"2008","unstructured":"Whitman SP, Ruppert AS, Radmacher MD, 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. 10.1182\/blood-2007-08-107946","journal-title":"Blood"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.612880","article-title":"FLT3 mutations in acute myeloid leukemia: key concepts and emerging controversies","volume":"10","author":"Kennedy VE","year":"2020","unstructured":"Kennedy VE, Smith CC. FLT3 mutations in acute myeloid leukemia: key concepts and emerging controversies. Front Oncol. 2020, 10:612880. 10.3389\/fonc.2020.612880","journal-title":"Front Oncol"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-024018","article-title":"Activation mechanisms of STAT5 by oncogenic Flt3-ITD","volume":"110","author":"Choudhary C","year":"2007","unstructured":"Choudhary C, Brandts C, Schwable J, et al.. Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Blood. 2007, 110:370-4. 10.1182\/blood-2006-05-024018","journal-title":"Blood"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1281-x","article-title":"Molecular targeting in acute myeloid leukemia","volume":"15","author":"Lim SH","year":"2017","unstructured":"Lim SH, Dubielecka PM, Raghunathan VM. Molecular targeting in acute myeloid leukemia. J Transl Med. 2017, 15:183. 10.1186\/s12967-017-1281-x","journal-title":"J Transl Med"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614359","article-title":"Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation","volume":"377","author":"Stone RM","year":"2017","unstructured":"Stone RM, Mandrekar SJ, Sanford BL, et al.. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017, 377:454-64. 10.1056\/NEJMoa1614359","journal-title":"N Engl J Med"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00464-6","article-title":"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","volume":"401","author":"Erba HP","year":"2023","unstructured":"Erba HP, Montesinos P, Kim HJ, et al.. 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. Lancet. 2023, 401:1571-83. 10.1016\/S0140-6736(23)00464-6","journal-title":"Lancet"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30416-3","article-title":"Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study","volume":"18","author":"Perl AE","year":"2017","unstructured":"Perl AE, Altman JK, Cortes J, et al.. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017, 18:1061-75. 10.1016\/S1470-2045(17)30416-3","journal-title":"Lancet Oncol"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30240-7","article-title":"Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial","volume":"19","author":"Cortes J","year":"2018","unstructured":"Cortes J, Perl AE, D\u00f6hner H, et al.. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018, 19:889-903. 10.1016\/S1470-2045(18)30240-7","journal-title":"Lancet Oncol"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/178475-flt3-mutations-in-acute-myeloid-leukemia-unraveling-the-molecular-mechanisms-and-implications-for-targeted-therapies","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T20:07:44Z","timestamp":1707509264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/178475-flt3-mutations-in-acute-myeloid-leukemia-unraveling-the-molecular-mechanisms-and-implications-for-targeted-therapies"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,22]]},"references-count":25,"URL":"https:\/\/doi.org\/10.7759\/cureus.45765","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9,22]]}}}