Hematologic Malignancy
Acute Myeloid Leukemia
CI-CAN-00001674AML · ANLLExplore in graph →
Hematologic789 active trials18 approved drugs279 evidence items
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Hematologic Malignancy
CI-CAN-00001674AML · ANLLExplore in graph →
Variants & evidence
525 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 F691L10 | ||||||||
| Lestaurtinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID8341A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified F691L. Cytotoxicity assessed by MTT demonstrated Ba/F3 cells expressing FLT3/IT… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID8342A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in the FLT3 TKI midostaurin identified F691L in 1 of 400 clones. Cytotoxicity assessed by MTT demonstra… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID8674Deep sequencing revealed that no secondary F691L mutations were found in all 9 patients who achieved a partial or complete response on PLX3397 and who subsequently relapsed on the drug, suggesting thi… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Does Not Support Resistance | 1 | rejected | EID9716Overall response rate was 21% in this clinical trial with Pexidartinib on relapsed or refractory AML patients with FLT3-ITD. Forty two out of the total 80 patients were tested for FLT3 KD mutations be… (full text at CIViC) PMID 32330242 · Smith et al., 2020 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Does Not Support Resistance | 1 | submitted | EID9717Overall response rate was 21% in this clinical trial with Pexidartinib on relapsed or refractory AML patients with FLT3-ITD. Forty two out of the total 90 patients were tested for FLT3 KD mutations be… (full text at CIViC) PMID 32330242 · Smith et al., 2020 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8664Proliferation studies revealed that PLX3397 has the ability to inhibit the proliferation of Ba/F3 cells expressing FLT3-ITD/F691L (IC50 = 0.097μM). PLX3397 equally inhibited the proliferation of MOLM1… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID9718Using AC220 (Quizartinib) treatment in Ba/F3 cell lines in a in vitro saturation mutagenesis assay, variants in four residues in FLT3 kinase domain were found, including E608, F691, D835 and Y842. Exc… (full text at CIViC) PMID 22504184 · Smith et al., 2012 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8843A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified F691L. Cytotoxicity assessed by MTT demonstrated Ba/F3 cells expressing FLT3/IT… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8845A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified F691L. Cytotoxicity assessed by MTT demonstrated Ba/F3 cells expressing FLT3/IT… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8844A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified F691L. Cytotoxicity assessed by MTT demonstrated Ba/F3 cells expressing FLT3/IT… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| FLT3 G697R1 | ||||||||
| K 252a + Midostaurin + SU5614Substitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID7604Constructs of Ba/F3 cell line containing the FLT3 open reading frame with an internal tandem duplication of (FLT3-ITD) were used to induce point mutations in the ATP binding pocket of FLT3. Constructs… (full text at CIViC) PMID 15374944 · Cools et al., 2004 · Open in CIViC | civic |
| FLT3 G697S2 | ||||||||
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Reduced Sensitivity | 4 | submitted | EID9022Gilteritinib is the first FLT3 inhibitor approved by the Food and Drug administration (FDA) as monotherapy in adult refractory/relapse acute myeloid leukemia (R/R AML) patients with FLT3-ITD and/or ty… (full text at CIViC) PMID 32040554 · Tarver et al., 2020 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8898Using in vitro proliferation assay in Ba/F3 cells, it was found that the cells with FLT3-ITD G697S exhibited potent resistance to Gilteritinib. Similar resistance was found in cells bearing FLT3-ITD F… (full text at CIViC) PMID 32040554 · Tarver et al., 2020 · Open in CIViC | civic |
| FLT3 I836S1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 2 | accepted | EID9782In this study, activating FLT3 mutations identified in patients with Acute Myeloid Leukemia were modeled using Ba/F3 cell lines generated by site-directed mutagenesis and transfection. These cells wer… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
| FLT3 I836T1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 2 | accepted | EID9783In this study, FLT3 activating mutations identified in patients with acute myeloid leukemia were modeled using murine Ba/F3 cells generated by site-directed mutagenesis and transfection. These cells w… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
| FLT3 ITD35 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | A | Supports Poor Outcome | 3 | accepted | EID190Meta-analysis of studies involving cytogentically normal younger (<60) patients showed reduced overall and relapse-free survival for patients with FLT3-ITD. PMID 24801015 · Port et al., 2014 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID69In AML patients with FLT3-ITD mutations, concurrent DNMT3A mutations were associated with worse overall survival compared to those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | |||||
Data updated 9 minutes 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.
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EID1515In the absence of a FLT3 (ITD) mutation, a co-mutation of NPM1 and DNMT3A had a 50% 10-year survival rate, whereas triple-mutation of NPM1, DNMT3A, and FLT3 (ITD) had a 20% 10-year survival rate. PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 4 | accepted | EID52In young AML patients (<60 years old), DNMT3A mutation status was not predictive of overall and relapse free survival in patients with NPM1 mutations and wildtype FLT3 or wildtype NPM1 and FLT3-ITD. PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID128FLT3-ITD mutation without NPM1 was associated with increased relapse risk and reduced overall survival in young adult AML patients (median age 43). PMID 17957027 · Gale et al., 2008 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 4 | accepted | EID158FLT3-ITD duplication length did not effect prognosis in patients with an NPM1 mutation. PMID 21537333 · Schnittger et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID191A ratio of >0.49 FLT3-ITD/FLT3 wildtype level was associated with reduced event-free and overall survival in old (>59) and younger patients (<60) with an NPM1 mutation. PMID 21537333 · Schnittger et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID192Patients with NPM1 mutation and FLT3-ITD had reduced event-free survival compared to patients with wildtype FLT3. PMID 21537333 · Schnittger et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID193Using a ratio of FLT3-ITD/FLT3 wildtype levels as a continuous variable, a higher ratio was associated with reduced event-free survival in patients with an NPM1 mutation. PMID 21537333 · Schnittger et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID195Coocurrence of FLT3-ITD mutations significantly reduced overall (N=74 vs 95, P=0.003) and disease-free survival (N=43 vs 67, P=0.02) of normal karyotype AML patients (<60 years old) compared to patien… (full text at CIViC) PMID 16455956 · Thiede et al., 2006 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID372Simultaneous tandem repeat of FLT3 with loss of wild type FLT3 leads to poor survival and inferior disease free survival in patients with AML. PMID 11585760 · Whitman et al., 2001 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9259The authors screened 979 acute myelogenous leukemia patients for FLT3 variants. FLT3-internal tandem duplication (FLT3-ITD) variants have been reported in 200 patients (20.4%). The study showed that h… (full text at CIViC) PMID 12036858 · Thiede et al., 2002 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID129Increasing level of FLT3-ITD mutant correlated with reduced disease-free and overall survival as well as increased relapse rate. PMID 17957027 · Gale et al., 2008 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID198Patients with NPM1 mutations and low (<25%, N=63), intermediate (25-50%, N=156) or high (>50%, N=66) levels of FLT3-ITD have worse overall survival (P<0.0001 for trend) and cumulative incidence of rel… (full text at CIViC) PMID 24855211 · Linch et al., 2014 · Open in CIViC | civic |
| (diagnostic) | Acute Myeloid LeukemiaCURATED_BROADER | Diagnostic | B | Supports Positive | 3 | accepted | EID222WBC counts were higher in AML patients with internal tandem repeat of Flt3 compared to wild type. PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC | civic |
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID371AML patients with internal tandem repeat of FLT3 has worse overall survival than patients with wild type FLT3. PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC | civic |
| 〃 | Acute Promyelocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1109In a study of 53 APL patients treated with combination ATRA/anthracycline chemotherapy, patients with the FLT3 ITD mutation (n=10) had higher rates of relapse (30% vs. 2.5%), lower rates of remission … (full text at CIViC) PMID 21461300 · Hong et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 2 | accepted | EID159Size of the FLT3-ITD mutant duplication had no impact on overall survival or relapse rate. PMID 17957027 · Gale et al., 2008 · Open in CIViC | civic |
| Anthracycline Antineoplastic Antibiotic + TretinoinCombination | Acute Promyelocytic Leukemia | Predictive | B | Supports Resistance | 4 | accepted | EID1112In a study of 171 APL patients treated with combination ATRA/anthracycline chemotherapy, FLT3 ITD mutations (n=35) were associated with lower 3-year OS compared to the FLT3 ITD-negative group (62% vs.… (full text at CIViC) PMID 24981688 · Lucena-Araujo et al., 2014 · Open in CIViC | civic |
| Daunorubicin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID130Ba/F3 cells with both FLT3-ITD and TKD mutations on the same allele have more resistance to daunorubicin than cells with FLT3-ITD alone. PMID 15626738 · Bagrintseva et al., 2005 · Open in CIViC | civic |
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID12621In a phase 3 trial comparing gilteritinib (120 mg/day) to salvage chemotherapy (SC) in adults with relapsed or refractory FLT3- mutated AML, patients were required to have FLT3 ITD or TKD (tyrosine ki… (full text at CIViC) PMID 31665578 · Perl et al., 2019 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID8924In vitro gilteritinib treatment of MV4-11 and MOLM-13 cells, which endogenously express FLT3-ITD, showed growth suppression based on CellTiter GLO cytotoxicity assays with IC50 values of 0.92 nM (95% … (full text at CIViC) PMID 28516360 · Mori et al., 2017 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID8923This study was designed to test the efficacy of FLT3 inhibitors in vitro against FLT3-ITD and other TKD variants clinically observed. IC50s were determined from immunoblots quantifying FLT3 phosphoryl… (full text at CIViC) PMID 27908881 · Lee et al., 2017 · Open in CIViC | civic |
| Hematopoietic Cell Transplantation + SorafenibSequential | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | submitted | EID9070This study was a randomised phase 3 trial to compare sorafenib maintenance with non-maintenance post-transplantation for patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoi… (full text at CIViC) PMID 32791048 · Xuan et al., 2020 · Open in CIViC | civic |
| Lestaurtinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID297CEP701 was effective in reducing blast counts of 5/14 heavily pre-treated AML patients with FLT3 mutations. PMID 14726387 · Smith et al., 2004 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | submitted | EID7061In a study of 717 newly diagnosed acute myeloid leukemia patients harboring FLT3 mutations (555 FLT3-ITD, 162 FLT3-TKD), patients were randomized to receive placebo or midostaurin. Patients receiving … (full text at CIViC) PMID 28644114 · Stone et al., 2017 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID8658Patients in the Beat AML published dataset (n= 214 (193 primary; 21 relapse AML)) samples were studied with an ex vivo drug sensitivity screen to test whether concomitant genomic alterations alter mid… (full text at CIViC) PMID 32754299 · Rosenberg et al., 2020 · Open in CIViC | civic |
| AG1295 + AGS324 + Crenolanib + FLT3 Tyrosine Kinase Inhibitor TTT-3002 + KW2449 + Lestaurtinib + Linifanib + Midostaurin + Ponatinib + Quizartinib + R406 + Sorafenib + SunitinibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11084A panel of FLT3 tyrosine kinase inhibitors was tested against Ba/F3 cells transfected with FLT3-ITD using MTT growth/survival assay. Each of the 13 TKIs inhibited proliferation of FLT3-ITD cells in a … (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
| PacritinibCombination | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID9217A phase I study of pacritinib in combination with cytarabine and daunorubicin (cohort A) or with decitabine induction (cohort B) in AML patients with FLT3 mutations. A total of thirteen patients were … (full text at CIViC) PMID 31102119 · Jeon et al., 2020 · Open in CIViC | civic |
| Ponatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 5 | accepted | EID7369In a preclinical trial, multiple experiments testing the effectiveness of ponatinib on the mutation FLT3-ITD in acute myeloid leukemia (AML) were conducted. Ponatinib was very effective in targeting t… (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC | civic |
| Selumetinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Resistance | 2 | accepted | EID1137Forty-seven patients with relapsed/refractory AML or 60+ years old with untreated AML were enrolled on a phase II study. In FLT3 wild-type patients, six out of 36 (17%) had a response (1 PR, 3 MR, 2 u… (full text at CIViC) PMID 24178622 · Jain et al., 2014 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID298Sorafenib is effective in patients with FLT3 internal tandem repeats, but not in wild type or D835 mutation. PMID 18230792 · Zhang et al., 2008 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID104013 patients with relapsed or chemo-refractory FLT3-ITD+ AML were treated with sorafenib (200-400 mg twice daily). 12 patients showed clearance or near clearance of bone marrow myeloblasts after 27 (ra… (full text at CIViC) PMID 22368270 · Man et al., 2012 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID1555Six children with relapsed or refractory FLT3-ITD-positive AML received initial therapy with sorafenib (alone or in combination with clofarabine and cytarabine). Four of the patients initially achiev… (full text at CIViC) PMID 23969938 · Baker et al., 2013 · Open in CIViC | civic |
| Hematopoietic Cell Transplantation + SorafenibSequential | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID9069The SORMAIN trial provides evidence that an inhibition of FLT3 through sorafenib significantly reduces the risk of relapse and death after allogeneic hematopoietic stem cell transplantation for FLT3-I… (full text at CIViC) PMID 32673171 · Burchert et al., 2020 · Open in CIViC | civic |