Cancer Family
Malignant Bone Marrow Neoplasm
CI-CAN-00000226Explore in graph →
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Cancer Family
CI-CAN-00000226Explore in graph →
Variants & evidence
1,124 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 D835Y8 | ||||||||
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID12620A 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 |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8108A 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 |
| Lestaurtinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID11095Ba/F3 cells with FLT3 D835Y were transplanted into mice. The cells were stably transfected with luciferase and this was used to monitor disease progression with luciferin injections to visualize biolu… (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 | EID11085A 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 |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12625A patient (29/M) had 2 weeks with oral cavity ulcer and nasal bleeding and was diagnosed with AML with marrow including 91.5 % blasts with morphologic features of AML-M5. Karyotype was abnormal (47, … (full text at CIViC) PMID 27408351 · Yue et al., 2016 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 4 | submitted | EID11096Ba/F3 cells with FLT3 D835Y were transplanted into mice. The cells were stably transfected with luciferase and this was used to monitor disease progression with luciferin injections to visualize biolu… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12813Ba/F3 cells expressing FLT3 D835Y and treated with sorafenib demonstrated a dose-dependent inhibition of cell proliferation. Ba/F3 cells transformed with FLT3 D835Y showed a 50% inhibition of cell pro… (full text at CIViC) PMID 17229632 · Lierman et al., 2007 · Open in CIViC | civic |
| Tandutinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12618MLN518 inhibited the proliferation of Ba/F3 cells transduced with FLT3 activation loop mutation D835Y (IC50 > 10 micromolar). In addition, MLN518 inhibited phosphorylation of FLT3, STAT5 and ERK. Trea… (full text at CIViC) PMID 15256420 · Clark et al., 2004 · Open in CIViC | civic |
| FLT3 D839A1 | ||||||||
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8671Mutations 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 D839A (IC50 = 4.0μM) and FL… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| FLT3 D839G2 | ||||||||
| (prognostic) | Acute Promyelocytic Leukemia | Prognostic | C | Supports Poor Outcome | 1 | submitted | EID8908This is a case report about an adult patient with acute promyelocytic leukemia (APL) who had relapse in a testicle prior to systemic relapse of APL. Retrospective analysis of the preserved samples fro… (full text at CIViC) PMID 23816818 · Zou et al., 2013 · Open in CIViC | civic |
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID8927Single strand polymorphism targeting FLT3 in addition to RUNX1, KIT, CEBPA, PTPN11, and NRAS was carried out to identify novel recurring gene mutations in an acute myeloid leukemia cohort comprised of… (full text at CIViC) PMID 15667533 · Smith et al., 2005 · Open in CIViC | civic |
| FLT3 D839H1 | ||||||||
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 2 | submitted | EID8673Mutations were identified by in vitro saturation mutagenesis on the background of FLT3-ITD. Proliferation studies showed that the FLT3-ITD D839H (IC50 = 8.6μM) confers relative resistance to PLX3397 i… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| FLT3 D839N1 | ||||||||
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8672Mutations 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 D839N (IC50 = 0.85μM) and F… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| FLT3 E573del1 | ||||||||
| Crenolanib + Lestaurtinib + Midostaurin + Ponatinib + Quizartinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9307The construct supported IL-3 independent growth of Ba/F3 cells. It showed FLT-3 autophosphorylation and downstream signaling via STAT5, AKT, and ERK1/2 pathways. With IL-3 deprivation, the cells showe… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| FLT3 E588_Y589INSKYFYVDFRE4 | ||||||||
| Palbociclib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4738In an in vitro study, MOLM-14, PL21 and MV4-11 cell lines expressing FLT3 internal tandem duplication mutation (FLT3-ITD) demonstrated increased sensitivity to palbociclib treatment, compared to THP-1… (full text at CIViC) PMID 27099147 · Uras et al., 2016 · Open in CIViC | civic |
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | — | submitted | EID4735In a retrospective study of 15 acute myeloid leukemia patients, the patients with FLT3 internal tandem duplication mutation (n=2) were associated with improved response to sunitinib treatment. The pat… (full text at CIViC) PMID 15459012 · Fiedler et al., 2005 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 E611_F612INS252 | ||||||||
| Palbociclib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4582In an in vitro study, MOLM-14, PL21 and MV4-11 cell lines expressing FLT3 internal tandem duplication mutation (FLT3-ITD) demonstrated increased sensitivity to palbociclib treatment, compared to THP-1… (full text at CIViC) PMID 27099147 · Uras et al., 2016 · Open in CIViC | civic |
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | — | submitted | EID4581In a retrospective study of 15 acute myeloid leukemia patients, the patients with FLT3 internal tandem duplication mutation (n=2) were associated with improved response to sunitinib treatment. The pat… (full text at CIViC) PMID 15459012 · Fiedler et al., 2005 · Open in CIViC | civic |
| FLT3 F691L13 | ||||||||
| Crenolanib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 5 | submitted | EID12387FLT3 F691L was observed in 2 patient samples collected after at least 28 days of treatment with crenolanib. Prior to treatment with crenolanib, both patients were treated with quizartinib. Ba/F3 cells… (full text at CIViC) PMID 30651561 · Zhang et al., 2019 · Open in CIViC | civic |
| FLT3/ABL/Aurora Kinase Inhibitor KW-2449 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8846A 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 |
| Gilteritinib | Acute Myeloid Leukemia | |||||||
| 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 G73E1 | ||||||||
| (oncogenic) | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Oncogenic | C | Supports Oncogenicity | 2 | rejected | EID12426The variant was identified by NGS in a CML (unmatched analysis) (Supplementary File 2). PMID 32943879 · Wu 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 ITD11 | ||||||||
| (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 18 hours 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 |
| C |
| Supports Sensitivity Response |
| — |
| submitted |
EID4736In a phase I study of 29 acute myeloid leukemia patients, patients with FLT3 internal tandem duplication (ITD) mutation (n=3) were associated with improved response to sunitinib monotherapy compared … (full text at CIViC) PMID 14654525 · O'Farrell et al., 2003 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4737In an in vitro study, leukemia M4;11 (endogenous), myeloid 32D (overexpression) and Chinese hamster ovary (transient expression) cell lines expressing FLT3 internal tandem duplication mutation demonst… (full text at CIViC) PMID 12531805 · O'Farrell et al., 2003 · Open in CIViC | civic |
| Predictive |
| D |
| Supports Resistance |
| 3 |
| submitted |
EID8562With Ba/F3 cells bearing FLT3-ITD F691L mutations and by in vitro proliferation assay, it was found that the cells exhibited >10-fold resistance to Gilteritinib. Similar resistance was found in cells … (full text at CIViC) PMID 32040554 · Tarver et al., 2020 · Open in CIViC |
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| 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 |
| 5 |
| accepted |
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 |