Hematologic Malignancy
Acute Leukemia
CI-CAN-00000399Explore in graph →
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Hematologic Malignancy
CI-CAN-00000399Explore in graph →
Variants & evidence
645 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| FLT3 D835Y + FLT3 ITD1 | ||||||||
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Resistance | 4 | accepted | EID247In a trial with 13 patients with relapsed or refractory FLT3-ITD AML, considered unfit for further induction chemotherapy, D835Y emerged during resistance in three cases with initial sorafenib respons… (full text at CIViC) PMID 22368270 · Man et al., 2012 · Open in CIViC | civic |
| FLT3 F691L + FLT3 ITD1 | ||||||||
| Tirbanibulin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9774Using molecular docking simulations, the authors computationally screened a library of clinical compounds and identified KX2-391(Tirbanibulin, an SRC/tubulin dual inhibitor) to be a candidate FLT3 inh… (full text at CIViC) PMID 34217323 · Wang et al., 2021 · Open in CIViC | civic |
| FLT3 ITD + KDM6A LossKDM6AFLT31 | ||||||||
| Olaparib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11035FLT3-ITD positive AML cells with lower KDM6A expression showed sensitivity to olaparib. | civic |
| FLT3 ITD D651G1 | ||||||||
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8910Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| FLT3 ITD & D835(V/Y/F/H)2 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID9141Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC) PMID 26438511 · Garg et al., 2015 · Open in CIViC | civic |
| Ponatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID8894Proliferation of Ba/F3 cells with FLT3 double mutations was studied for the activity of ponatinib. Compared to control cells with native FLT3-ITD mutant (IC50: 3.0nM), cells with double mutants, FLT3-… (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC | civic |
| FLT3 ITD & D839G4 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID9140Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC) PMID 26438511 · Garg et al., 2015 · Open in CIViC | civic |
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8669Mutations were identified by in vitro saturation mutagenesis on the background of FLT3-ITD or FLT3-ITD/F691L. Proliferation and biochemical studies showed that the FLT3-ITD D839G (IC50 =4.1μM) and FLT… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 ITD&F691(I/L)3 | ||||||||
| Ningetinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12432Ningetinib inhibited Ba/F3 cells with FLT3 ITD-F691L in cell proliferation assays. FLT3-ITD-F691L cells treated with ningetinib for 6 hours demonstrated inhibition of FLT3 phosphorylation and also pho… (full text at CIViC) PMID 38978049 · Hu et al., 2024 · Open in CIViC | civic |
| Ponatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID8893Proliferation of Ba/F3 cells with FLT3 double mutations was studied for the activity of ponatinib. Compared to control cells with native FLT3-ITD mutant (IC50: 3.0nM), cells with double mutants (FLT3-… (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 ITD I687F1 | ||||||||
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8912Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| FLT3 ITD & L601F1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID9143Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC) PMID 26438511 · Garg et al., 2015 · Open in CIViC | civic |
| FLT3 ITD N676D1 | ||||||||
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8911Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafanib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| FLT3 ITD N676K2 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID9144Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC) PMID 26438511 · Garg et al., 2015 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Resistance | 3 | submitted | EID7524In a study looking for mechanisms of resistance within a phase 2 study using PKC412 (midostaurin), a 60 year old male with normal karyotype AML was identified with FLT3-ITD-N676K mutation. This mutati… (full text at CIViC) PMID 16150941 · Heidel et al., 2006 · Open in CIViC | civic |
| FLT3 ITD & N841K1 | ||||||||
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID9936Using a saturation mutagenesis screen, resistant clones harboring N841K were identified in a Ba/F3 proliferation assay when exposed to PLX3397 on a FLT3-ITD + F691L background (Figure 3B). The N841K m… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| FLT3 D835 + FLT3 I836 + FLT3 ITD2 | ||||||||
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7728In this phase 3 trial (ADMIRAL), 371 patients with relapsed or refractory FLT3-mutated AML (required to have FLT3 ITD or TKD D835 or I836 mutations) were randomly assigned in a 2:1 ratio to receive ei… (full text at CIViC) PMID 31665578 · Perl et al., 2019 · Open in CIViC | civic |
| Chemotherapy + MidostaurinCombination | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11261In this phase III randomized, double-blind placebo-controlled trial, 717 patients with FLT3 mutations (tested for ITD or 835 or 836) underwent randomization 1:1 such that 360 were assigned to the mido… (full text at CIViC) PMID 28644114 · Stone et al., 2017 · Open in CIViC | civic |
| FLT3 ITD + FLT3 TKD MUTATION + KRAS Exon 2-3 Mutation + NRAS EXON 2-3 MUTATION + PTPN11 MutationFLT3NRASPTPN11KRAS1 | ||||||||
| Selumetinib | Acute Lymphoblastic Leukemia | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12553In a preclinical genomic and functional study of pediatric acute lymphoblastic leukemia (n = 81 paired diagnosis–relapse samples), recurrent RAS-pathway mutations involving NRAS (exons 2-3), KRAS (exo… (full text at CIViC) PMID 24316979 · Wong et al., 2014 · Open in CIViC | civic |
| FLT3 ITD & TKD MUTATIONS2 | ||||||||
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID8516A Phase III Randomized, Double-Blind study of chemotherapy + Midostaurin or Placebo in newly diagnosed patients < 60 Years of age with FLT3 mutated Acute Myeloid Leukemia (AML). Overall survival was s… (full text at CIViC) PMID 28644114 · Stone et al., 2017 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8914Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| FLT3 ITD & Y597F1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID9142Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC) PMID 26438511 · Garg et al., 2015 · Open in CIViC | civic |
| FLT3 ITD & Y842C4 | ||||||||
| FLT3 Inhibitor FF-10101 Succinate | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9082By assessing cell viability using MTS assay, FF-10101 showed growth inhibitory effects on FLT3-ITD with Y842C mutation expressing 32D cells(Figure 3A). Consistently, FF-10101 potently inhibited FLT3 p… (full text at CIViC) PMID 29187377 · Yamaura et al., 2018 · Open in CIViC | civic |
| Ponatinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID8895Proliferation of Ba/F3 cells with FLT3 double mutations was studied for the activity of ponatinib and sorafenib. Compared to control cells with native FLT3-ITD mutant (IC50: 3.0nM), cells with double … (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC | civic |
| FLT3 K663Q1 | ||||||||
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8670From 109 unselected AML patients, one was identified to harbor a FLT3 K663Q mutation in the TK1 domain [outside the juxtamembrane (JM) domain and the activation loop (AL)], homologous to the KIT K642E… (full text at CIViC) PMID 16990784 · Schittenhelm et al., 2006 · Open in CIViC | civic |
| FLT3 M664I1 | ||||||||
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8667Mutations were identified by in vitro saturation mutagenesis on the background of FLT3-ITD or FLT3-ITD/F691L. Proliferation and biochemical studies showed that the FLT3-ITD M664I (IC50 =0.61μM) and FL… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| FLT3 M737I1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Does Not Support Oncogenicity | 3 | accepted | EID12961FLT3 M737I variant was found in patient at diagnosis but absent in the remission sample. BaF3 cells was transformed to express M737I and these cells were unable to grow in the absence of IL-3 similar … (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| FLT3 Mutation7 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID8266In this cohort, 431 patients (537 specimens underwent targeted NGS, 68 patients underwent more than one sequencing reaction) with an AML diagnosis (new and r/r) were analyzed to identify and character… (full text at CIViC) PMID 30181385 · Schwartz et al., 2019 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 2 | accepted | EID156FLT3 mutations did not alter overall survival or remission duration in younger (16-60), cytogenetically normal AML patients with CEBPA mutations. 10/36 patients with CEBPA mutations also had FLT3 muta… (full text at CIViC) PMID 14726504 · Fröhling et al., 2004 · Open in CIViC | civic |
| Unspecified therapy | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 N676K1 | ||||||||
| Midostaurin + QuizartinibSequential | Core Binding Factor Acute Myeloid Leukemia | Predictive | B | Supports N/A | 3 | submitted | EID8263In a cohort of 84 de novo AML patients with a CBFB/MYH11 rearrangement and in 36 patients with a RUNX1/RUNX1T1 rearrangement, the FLT3 N676K mutation was identified in 5 and 1 patients, respectively (… (full text at CIViC) PMID 23878140 · Opatz et al., 2013 · Open in CIViC | civic |
| FLT3 N841I9 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 1 | submitted | EID9235This study identified genetic driver mutations by sequencing 111 genes and cytogenetic studies in 1540 samples across three different clinical trials. Table S5 shows all mutations identified in the sa… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12507In 65 hematologic cancer patient samples (53 AML, 9 ALL, and 3 MDS) partially enriched for lacking FLT3 ITD mutations, resequencing of 21/24 FLT3 exons was performed. In 2 patients with AML, the novel… (full text at CIViC) PMID 15178581 · Jiang et al., 2004 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with NPM1 MutationALIAS | |||||||
| FLT3 N841K1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 4 | submitted | EID9236This study identified genetic driver mutations by sequencing 111 genes and cytogenetic studies in 1540 samples across three different clinical trials. The prognostic significance of FLT3 tyrosine kina… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
Data updated 1 hour agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Predictive |
| D |
| Supports Sensitivity Response |
| 4 |
| submitted |
EID8896Proliferation of Ba/F3 cells with FLT3 double mutations was studied. Compared to control cells with native FLT3-ITD mutant (IC50: 0.13-3.0nM), cells with double mutants (FLT3-ITD/D839G) were sensitive… (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC |
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| Ponatinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID8897Proliferation of Ba/F3 cells with FLT3 double mutations was studied. Compared to control cells with native FLT3-ITD mutant (IC50: 0.13-3.0nM), cells with double mutants (FLT3-ITD/D839G) were sensitive… (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC | civic |
| Predictive |
| D |
| Supports Resistance |
| 3 |
| submitted |
EID9779The F691L/I mutation in FLT3 kinase domain conferred resistence to AC220 (Quizartinib). These mutations were identified by in vitro screening assays and from AML patients who developed resistance to Q… (full text at CIViC) PMID 22875611 · Pauwels et al., 2012 · Open in CIViC |
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| Acute Myeloid LeukemiaCURATED_BROADER |
| Predictive |
| D |
| Supports Resistance |
| 4 |
| submitted |
EID9081To study pro-apoptotic effects against AML cells harboring FLT3-ITD and/or TKD mutations by selinexor, apoptosis induction was assessed as the percentage of annexin V–positive cells by flow cytometry.… (full text at CIViC) PMID 29773601 · Zhang et al., 2018 · Open in CIViC |
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| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID8913Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| Predictive |
| C |
| Supports N/A |
| 2 |
| submitted |
EID8888In this retrospective analysis of 7 diagnostic specimens from patients with AML-Normal Karyotype (AML-NK), which also included 2 remission specimens and 1 relapse specimen (n =10), described a targete… (full text at CIViC) PMID 23702683 · Conte et al., 2013 · Open in CIViC |
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| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7283In a phase 1/2 trial, patients with refractory or relapsed AML with FLT3 mutation (n=191; ITD n=162, D835 n=13, ITD-D835 n=16) received gilteritinib. 49% (93/191) of patients achieved an overall respo… (full text at CIViC) PMID 28645776 · Perl et al., 2017 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID5261Midostaurin is FDA-approved for the treatment of newly-diagnosed acute myeloid leukemia patients harboring FLT3 mutations. PMID 28546144 · Levis, 2017 · Open in CIViC | civic |
| Nilotinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID5575Of the 14 AML patients receiving nilotinib, 80% achieved complete remission or complete remission with incomplete platelet recovery. Genetic testing revealed that 27% of these individuals conferred a … (full text at CIViC) PMID 28720666 · Shen et al., 2017 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID5574Compared to non-treated control cells, MV4-11 cells (FLT3 mutated cell line) that were exposed to nilotinib (30 uM) showed a 58% reduction in colony numbers.Further evidence to support cell death incl… (full text at CIViC) PMID 28720666 · Shen et al., 2017 · Open in CIViC | civic |
| Oncogenic |
| C |
| Supports Oncogenicity |
| 1 |
| submitted |
EID12508To study the mutational spectrum in older AML patients over, 22 cases of NPM1-mutated de novo AML in patients older than 75 were sequenced and 76 mutations (50 different variants) were found across 16… (full text at CIViC) PMID 33711909 · Pettersson et al., 2021 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12509Mutational profiling was performed with targeted NGS of 43 genes to analyze potential factors related to response and outcome in older patients with AML at the time of diagnosis enrolled in the FLUGAZ… (full text at CIViC) PMID 34070172 · Ayala et al., 2021 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID12506In 2 patients with AML, the novel N841I point mutation was detected by Sanger and Mass spectrometry genotyping. FLT3 N841I was placed into and expressed in Ba/F3 cells, which lead to IL-3 independent … (full text at CIViC) PMID 15178581 · Jiang et al., 2004 · Open in CIViC | civic |
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12510Ba/F3 cells were manipulated to express FLT3-ITD or the FLT3 Tyrosine Kinase Domain point mutation N841I. These cells were treated with the FLT3 inhibitor, gilteritinib, for 2 days and subsequently ce… (full text at CIViC) PMID 40196870 · Nakazawa et al., 2025 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID8858Expression of the N841I variant in murine BaF3 cell line resulted in constitutive autophosphorylation of FLT3 and the amount of autophosphorylated FLT3 was decreased with exposure to the FLT3 inhibito… (full text at CIViC) PMID 15178581 · Jiang et al., 2004 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12512Ba/F3 cells were manipulated to express FLT3-ITD or the FLT3 Tyrosine Kinase Domain point mutation N841I. These cells were treated with the FLT3 inhibitor, midostaurin, for 2 days and subsequently cel… (full text at CIViC) PMID 40196870 · Nakazawa et al., 2025 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12511Ba/F3 cells were manipulated to express FLT3-ITD or the FLT3 Tyrosine Kinase Domain point mutation N841I. These cells were treated with the FLT3 inhibitor, quizartinib, for 2 days and subsequently cel… (full text at CIViC) PMID 40196870 · Nakazawa et al., 2025 · Open in CIViC | civic |