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 | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|
| DNMT3A Mutation1 | |||||||
| Decitabine | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1587Among 46 AML patients treated with decitabine, the response rate was 75% (6/8) among DNMT3A mutated and 34% (13/38) among DNMT3A wild-type patients (P=.008) PMID 22124213 · Metzeler et al., 2012 · Open in CIViC | civic |
| DNMT3A R88228 | |||||||
| (prognostic) | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID62AML patients with DNMT3A mutations (59% of which were R882) showed worse survival (event-free and overall) outcome than those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID64In AML patients with FLT3-ITD mutations, concurrent DNMT3A mutations (including R882) were associated with worse overall survival compared to those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID65In cytogenetically normal AML patients, DNMT3A R882 mutations are associated with lower overall and disease free survival as compared to patients with wild type DNMT3A. PMID 24512939 · El Ghannam et al., 2014 · | |
| DNMT3A R882P1 | |||||||
| (diagnostic) | Diagnostic | B | Supports Positive | 5 | submitted | EID7228DNMT3A R882P somatic mutation, together with R882H, R882C and R882S were identified from Acute Myeloid Leukemia (AML) patients. And R882P, R882H and R882C were revealed as significant hotspot mutation… (full text at CIViC) PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| ABL2 Fusion1 | |||||||
| (oncogenic) | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12491The HT93A cell line was established from a patient with acute myelogenous leukemia (AML-M3). The patient was a 66 yr old man and was successfully induced to first and second remission with combined ch… (full text at CIViC) PMID 10706884 · Iijima et al., 2000 · Open in CIViC | civic |
| NTRK2 Fusion1 | |||||||
| Larotrectinib | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID6396Rearrangements involving the neurotrophic receptor kinase genes (NTRK1, NTRK2, and NTRK3; hereafter referred to as TRK) produce oncogenic fusions in a wide variety of cancers in adults and children. I… (full text at CIViC) PMID 29920189 · Taylor et al., 2018 · Open in CIViC | civic |
| NTRK3 Fusion1 | |||||||
| Entrectinib | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID7994Two AML cell lines, IMS-M2 and M0-91, with the ETV6-NTRK3 fusion were treated with entrectinib. Sequencing of these cell lines found no other driver mutations in 265 other cancer genes suggesting the… (full text at CIViC) PMID 29237803 · Smith et al., 2018 · Open in CIViC | civic |
| FGF2 EXPRESSION1 | |||||||
| Quizartinib | Predictive | D | Supports Resistance | 4 | accepted | EID1711AML MOLM14 cells were cocultured with FLT3 inhibitor AC220 (10 nM) and selected proteins expressed in the bone marrow microenvironment. FL and FGF2 were the only proteins that increased viability >2 s… (full text at CIViC) PMID 27671675 · Traer et al., 2016 · Open in CIViC | civic |
| FGFR1 Fusion1 | |||||||
| Ponatinib | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID7380In this preclinial trial, the AML cell line KG1 with FGFR1OP2-FGFR1 mutation was treated with Ponatinib. This drug effectively inhibits both FGFR phosphorylation and viability for KG1 cells at IC50 va… (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC | civic |
| PDGFRA Fusion3 | |||||||
| Ponatinib | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID7381In this preclinial trial, the AML cell line EOL1 with FIP1L1-PDGFR alpha mutation was treated with Ponatinib. This drug effectively inhibits both PDGFR phosphorylation and viability for EOL1 cells at … (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC | civic |
| Sorafenib | Predictive | D | Supports Sensitivity Response | 3 | rejected | EID7377In a preclinical trial, EOL1 AML cell lines with the FIP1L1-PDGFRa fusion mutation were treated with the tyrosine kinase inhibitors (TKI) ponatinib, sorafenib, and sunitinib. Ponatinib was similarly e… (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC | civic |
| Sorafenib + SunitinibSubstitutes | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID7378 | |
| FLT3 D593del2 | |||||||
| Linifanib + Quizartinib + Sorafenib + SunitinibSubstitutes | Predictive | D | Does Not Support Sensitivity Response | 3 | submitted | EID11094A 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 | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID11093A 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 D8358 | |||||||
| Gilteritinib | Predictive | B | Supports Sensitivity Response | 1 | rejected | EID8333In 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 | Predictive | D | Supports Resistance | 3 | accepted | EID1036An 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 | Predictive | B | Supports Resistance | 4 | accepted | EID103913 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… | |
| FLT3 D835E1 | |||||||
| Sunitinib | Predictive | C | Supports Sensitivity Response | — | submitted | EID4021In 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 |
| FLT3 D835G1 | |||||||
| (oncogenic) | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11092D835G was originally identified from an AML patient. Transfection of D835G into Ba/F3 cells led to IL3 independent growth, indicating an oncogenic driver effect for the variant in these cells. This ev… (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
Data updated 20 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.
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| (diagnostic) | Diagnostic | B | Supports Positive | 5 | accepted | EID112DNMT3A mutations (59% of which were R882) were associated with an intermediate risk cytogenetic profile, normal cytogenetic profile, and M4 and M5 FAB subtypes. PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| (prognostic) | Prognostic | B | Does Not Support Poor Outcome | 4 | accepted | EID24There is no difference in the complete remission rate of de novo AML patients with DNMT3A mutation compared to those who are wild type for DNMT3A. PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID25De novo AML patients with DNMT3A D882 mutation showed worse survival (event-free and overall) outcome than those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| 〃 | Prognostic | B | Does Not Support N/A | 4 | accepted | EID51In young AML patients (<60 years old), DNMT3A mutation status (60% of which were R882) was not predictive of overall and relapse free survival in patients with NPM1 mutations and wildtype FLT3 or wild… (full text at CIViC) PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID66In older cytogenetically normal AML patients (>59 years), DNMT3A R882 mutation is prognostic for shorter disease free survival and overall survival compared to patients without the mutation. PMID 22291079 · Marcucci et al., 2012 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID67In young AML patients (<60 years old), DNMT3A mutations were associated with significantly reduced overall survival and relapse free survival in patients wildtype for NPM1 and FLT3. PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID68In younger cytogenetically normal AML patients (<60 years), DNMT3A mutations other than R882 are prognostic for shorter disease free survival and overall survival compared to patients without the muta… (full text at CIViC) PMID 22291079 · Marcucci et al., 2012 · Open in CIViC | civic |
| 〃 | Prognostic | B | Does Not Support N/A | 4 | accepted | EID157Complete remission rates did not differ between patients with wildtype or mutant DNMT3A (62% of which affected R882) and cytogenetically normal AML. PMID 22291079 · Marcucci et al., 2012 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID187DNMT3A mutations (62% of which were R882) were associated with reduced disease-free survival in patients with cytogenetically normal AML. PMID 22291079 · Marcucci et al., 2012 · Open in CIViC | civic |
| (diagnostic) | Diagnostic | B | Supports Positive | 3 | accepted | EID4Young AML patients (<60 years old) with DNMT3A mutations (60% of which were R882) were older in age, had higher white blood cell counts and had higher platelet counts than patients wildtype for DNMT3A… (full text at CIViC) PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC | civic |
| 〃 | Diagnostic | B | Supports Positive | 3 | accepted | EID31DNMT3A R882 mutations were associated with older age, higher white blood cell count, and FAB M4 and M5 subtypes compared to wildtype DNMT3A in a cohort of cytogenetically normal AML patients. PMID 24512939 · El Ghannam et al., 2014 · Open in CIViC | civic |
| (prognostic) | Prognostic | B | Does Not Support N/A | 3 | accepted | EID49In a large cohort of AML patients (mean = 48 years), DNMT3A mutation (64.5% of which were R882) had no prognostic value on overall, relapse free and event free survival. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| 〃 | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID50In a large cohort (n=1770) of AML patients (18-60 years old), DNMT3A mutation status (65.4% of which were R882) had no prognostic value for overall, relapse free and event free survival. This was true… (full text at CIViC) PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID61In a large cohort of young AML patients (18-60 years old), DNMT3A R882 mutations were associated with reduced relapse free survival in the entire cohort as well as the subset of patients with cytogene… (full text at CIViC) PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID63DNMT3A R882 mutation was associated with reduced relapse free and overall survival in ELN-unfavorable, cytogenetically normal AMLs. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| (diagnostic) | Diagnostic | B | Supports Negative | 3 | accepted | EID110Therapy-related AML was less common in patients with DNMT3A mutations (64.5% of which were R882) than patients wildtype for DNMT3A in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| 〃 | Diagnostic | B | Supports Positive | 3 | accepted | EID114DNMT3A mutations (64.5% R882) were associated with older age, higher white blood cell count and cytogenetically normal AML in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| 〃 | Diagnostic | B | Supports Positive | 3 | accepted | EID115DNMT3A R882 mutations were associated with cytogenetically normal AML in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| (prognostic) | Prognostic | B | Supports Better Outcome | 3 | accepted | EID170DNMT3A mutations were associated with achievement of complete remission in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID186Complete remission rate was not different between young AML patients (<60 years old) with or without DNMT3A mutations (60% of which were R882). PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC | civic |
| 〃 | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID189Young AML patients (415 patients; <60 years old) with DNMT3A R882 mutations (n=58) have shorter overall and relapse-free survival than patients with wildtype DNMT3A. PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC | civic |
| (diagnostic) | Diagnostic | B | Supports Positive | 2 | rejected | EID3DNMT3A R882 mutations occur most often in de novo AML patients with intermediate risk cytogenetics (39/194 intermediate risk patients vs 0/89 low and high risk). PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC | civic |
| (prognostic) | Prognostic | B | Does Not Support Better Outcome | 2 | accepted | EID113DNMT3A mutations (59% of which were R882) were associated with intermediate risk cytogenetics (including normal karyotype) and not favorable risk cytogenetic abnormalities (PML::RARA, RUNX1::RUNX1T1, … (full text at CIViC) PMID 21067377 · Ley et al., 2010 · Open in CIViC | civic |
| Daunorubicin | Predictive | B | Does Not Support Resistance | 4 | accepted | EID11Daunorubicin treatment resulted in similar overall survival and disease free survival in de novo AML patients with DNMT3A R882 mutation compared to those who do not harbor this mutation. PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC | civic |
| Idarubicin | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID18Idarubicin increases the overall survival and disease free survival in de novo AML patients with DNMT3A R882 mutation compared to those who do not harbor this mutation. PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC | civic |
In a preclinical trial, the AML cell line EOL1with the FIP1L1-PDGFRa fusion mutation was treated with the tyrosine kinase inhibitors (TKI) ponatinib, sorafenib, and sunitinib. Ponatinib was similarly … (full text at CIViC)
PMID 21482694 · Gozgit et al., 2011 · Open in CIViC
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PMID 22368270 · Man et al., 2012 · Open in CIViC
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| Quizartinib + SorafenibSubstitutes | Predictive | B | Supports Resistance | 4 | accepted | EID1038In 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 | Predictive | D | Supports Resistance | 3 | accepted | EID1037An 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 | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID4024In 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 |
| 〃 | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID4025In 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 |
| 〃 | Predictive | D | Supports Sensitivity Response | 1 | submitted | EID4026In 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 |