Gene

FLT3

fms related receptor tyrosine kinase 3

Explore in graph →CI-GENE-00002044HGNC:3765 ENSG00000122025 NCBI 2322 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (266)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–50 of 266 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
FLT3 Fusion1
(diagnostic)	Myeloid/Lymphoid NeoplasmUNRESOLVED	Diagnostic	C	Supports Positive	4	submitted

Cohorts

Alteration frequency by cohort (125)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved125 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Acute Myeloid Leukemia (OHSU, Cancer Cell 2022) aml_ohsu_2022	Acute Myeloid Leukemia	Ssm	278

Literature

Linked publications (46)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 46 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.
· N Engl J Med · 2019 · PMID 31665578 · validated civic_curation pubmed
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.
· Ann Hematol · 2014 · PMID 24801015 · validated civic_curation pubmed
Midostaurin approved for FLT3-mutated AML.
· Blood · 2017 · PMID 28546144 · validated civic_curation pubmed
DNMT3A mutations in acute myeloid leukemia.
· N Engl J Med · 2010 · PMID 21067377 · validated civic_curation pubmed

FLT3 Fusion3
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	4	submitted	EID13110 This study showed that when HLH domain of ETV6 (also known as TEL) fused to the cytoplasmic domain of the wild-type FLT3 receptor, the fusion caused oligomerization and activation of FLT3. The constit… (full text at CIViC) PMID 11021752 · Tse et al., 2000 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	4	submitted	EID13111 In this study ETV6::FLT3 (also known as TEL-ETV6) construct mimicking this fusion protein was used to generate transgenic mice. This study showed that constitutively active ETV6::FLT3 expression in tr… (full text at CIViC) PMID 17268528 · Baldwin et al., 2007 · Open in CIViC	civic
Transplantation	Myeloid/Lymphoid NeoplasmUNRESOLVED	Predictive	C	Supports Sensitivity Response	3	submitted	EID13099 This study highlights the potential efficacy of allogeneic stem-cell transplantation (allo-SCT) in ETV6::FLT3-positive myeloid/lymphoid neoplasm with eosinophilia. A 33-year-old man presented with lym… (full text at CIViC) PMID 23873282 · Chonabayashi et al., 2014 · Open in CIViC	civic

FLT3 Fusion3

(functional)

—UNRESOLVED

Functional

Supports Gain Of Function

submitted

EID13110

This study showed that when HLH domain of ETV6 (also known as TEL) fused to the cytoplasmic domain of the wild-type FLT3 receptor, the fusion caused oligomerization and activation of FLT3. The constit… (full text at CIViC)

PMID 11021752 · Tse et al., 2000 · Open in CIViC

FLT3 Amplification3
Regorafenib Anhydrous	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Does Not Support Sensitivity Response	3	submitted	EID7102 A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial resp… (full text at CIViC) PMID 27906677 · Lim et al., 2017 · Open in CIViC	civic
Sorafenib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	submitted	EID7103 Treatment with sorafenib of a patient with metastatic colorectal cancer and FLT3 translocation who had previously been heavily treated showed significant symptomatic and laboratory improvement with so… (full text at CIViC) PMID 25848357 · Moreira et al., 2015 · Open in CIViC	civic
Sunitinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID11667 A clinical study in 10 patients with Colorectal Cancer with FLT-3 amplification treated with Sunitinib. Two patients achieved SD, however one of the patients died due to disease progression. A PFS of … (full text at CIViC) PMID 33068284 · Al Baghdadi et al., 2020 · Open in CIViC	civic

FLT3 D593del2
Linifanib + Quizartinib + Sorafenib + SunitinibSubstitutes	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID11094 A panel of 13 FLT3 tyrosine kinase inhibitors was tested against Ba/F3 cells transfected with FLT3 D593del using MTT growth/survival assay, and results were compared to Ba/F3 cells transfected with FL… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC	civic
Crenolanib + FLT3 Tyrosine Kinase Inhibitor TTT-3002 + Lestaurtinib + MidostaurinSubstitutes	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID11093 A panel of 13 FLT3 tyrosine kinase inhibitors was tested against Ba/F3 cells transfected with FLT3 D593del using MTT growth/survival assay, and results were compared to Ba/F3 cells transfected with FL… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC	civic

FLT3 D8359
(prognostic)	Myelodysplastic SyndromeCURATED_BROADER	Prognostic	C	Supports Poor Outcome	2	accepted	EID8330 In a study of 82 newly diagnosed myelodysplastic syndrome (MDS) patients followed through to progression to acute myeloid leukemia (AML) (n =70), the incidence of FLT3 (ITD, TKD) and NRAS mutations at… (full text at CIViC) PMID 14737077 · Shih et al., 2004 · Open in CIViC	civic
Gilteritinib	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	1	rejected	EID8333 In a Phase 1-2 trial of patients with relapsed / refractory AML, patients were enrolled in 7 dose-escalation or dose-expansion cohorts. Gilteritinib monotherapy was well tolerated, generated high resp… (full text at CIViC) PMID 28645776 · Perl et al., 2017 · Open in CIViC	civic
Ponatinib + QuizartinibSubstitutes	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1036 An in-vitro saturation mutagenesis screen of 50 independently derived FLT3-ITD clones was performed to identify mutations that confer resistance to ponatinib. Mutations at 3 AL residues (D835 [n = 31]… (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC	civic
Sorafenib	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	B	Supports Resistance	4	accepted	EID1039 13 patients with relapsed or chemo-refractory FLT3-ITD+ AML were treated with sorafenib (200-400 mg twice daily). 12 patients responded, but sorafenib response was lost in most patients after 72 (rang… (full text at CIViC) PMID 22368270 · Man et al., 2012 · Open in CIViC	civic
Quizartinib + SorafenibSubstitutes	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	B	Supports Resistance	4	accepted	EID1038 In an in-vitro study using an in vitro saturation mutagenesis assay, 4 residues with AC220 (quizartinib) resistance-conferring mutations in the kinase domain of FLT3-ITD were identified. Mutations at … (full text at CIViC) PMID 22504184 · Smith et al., 2012 · Open in CIViC	civic
SU5614	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1037 An in-vitro cell-based screening approach generated FLT3-ITD-expressing cell lines resistant to the FLT3 inhibitors SU5614, PKC412, and sorafenib. SU5614 resistance mutations were limited to exchanges… (full text at CIViC) PMID 19318574 · von Bubnoff et al., 2009 · Open in CIViC	civic
Sunitinib	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	1	submitted	EID4024 In a retrospective study of 15 acute myeloid leukemia patients, the patients with FLT3 D835 mutation (n=2) were associated with improved response to sunitinib treatment (2/2 vs. 2/7) compared to FLT3 … (full text at CIViC) PMID 15459012 · Fiedler et al., 2005 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	1	submitted	EID4025 In a phase I study of 29 acute myeloid leukemia patients, a patient with FLT3 D835Y mutation was associated with responsiveness to sunitinib monotherapy. After failure of first-line chemotherapy, the … (full text at CIViC) PMID 14654525 · O'Farrell et al., 2003 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	1	submitted	EID4026 In an in vitro study, Chinese hamster ovary cells transiently expressing FLT3 D835Y mutation demonstrated sensitivity to sunitinib treatment (IC50: 30-300nM) similar to Chinese hamster ovary cells exp… (full text at CIViC) PMID 12531805 · O'Farrell et al., 2003 · Open in CIViC	civic

FLT3 D835Y8
(oncogenic)	Acute Myeloid LeukemiaCURATED_BROADER	Oncogenic	D	Supports Oncogenicity	3	submitted	EID12617 Cos7 cells transfected with mutant FLT3 D835Y cDNA demonstrated FLT3 ligand-independent tyrosine phosphorylation. 32D cells stably expressing mutant FLT3 D835Y proliferated without either IL-3 or reco… (full text at CIViC) PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Oncogenic	D	Supports Oncogenicity	2	submitted	EID12812 Ba/F3 cells expressing FLT3 D835Y were stably transfected, cultured for 48 hours and then cell viability was analyzed. Wild-type FLT3 cells grown with IL-3 or in the absence of IL-3 served as positive… (full text at CIViC) PMID 29372308 · Marhäll et al., 2018 · Open in CIViC	civic
6-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl)-N-(4-(methylsulfonyl)phenyl)pyridin-2-amine	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID12824 Imidazo [1,2-a]pyridine derivative 6-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl)-N-(4-(methylsulfonyl)phenyl)pyridin-2-amine showed inhibitory effects on cell proliferation in MOLM14 cell… (full text at CIViC) PMID 38056299 · Wang et al., 2024 · Open in CIViC	civic
AG1295 + AGS324 + KW2449 + Linifanib + Ponatinib + Quizartinib + R406 + Sorafenib + SunitinibSubstitutes	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID11086 A panel of 13 FLT3 tyrosine kinase inhibitors was tested against Ba/F3 cells transfected with FLT3 D835Y using MTT growth/survival assay, and results were compared to Ba/F3 cells transfected with FLT3… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC	civic
FLT3 Inhibitor FF-10101 Succinate	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID8111 Second level inhibitor FF-10101 was used to measure the inhibition of FLT3 kinase activity due to the potential for patients with the D835Y mutation to have a relapse in AML after first-generation mon… (full text at CIViC) PMID 29187377 · Yamaura et al., 2018 · Open in CIViC	civic
Gilteritinib	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	submitted	EID12620 A 60 year old female relapsed or refractory AML patient, white, and 55.2 kg, with favorable cytogenetic risk status Inv(16), and blast percentage of 95, had D835Y at time of bone marrow screening. Var… (full text at CIViC) PMID 32040554 · Tarver et al., 2020 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	4	accepted	EID8106 Gilteritinib inhibited the cell growth of Ba/F3 cells expressing D835Y (IC50 1.6 nM; 95% CI: 1.1–2.4 nM) compared to controls (IC50 420nM; 95% CI: 350–500 nM). Additionally, immunoblots showed gliteri… (full text at CIViC) PMID 28516360 · Mori et al., 2017 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID8108 A 35 year-old male patient (AML4) presented with a FLT3-ITD mutation at diagnosis and was refractory to induction and salvage chemotherapy. He then received quizartinib and underwent allogenic transpl… (full text at CIViC) PMID 27908881 · Lee et al., 2017 · Open in CIViC	civic