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Variants & evidence
1,079 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 |
|---|---|---|---|---|---|---|---|---|
| IDH1 R132C1 | ||||||||
| Ivosidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID2331In a clinical study of 17 relapsed or refractory AML patients harboring IDH1 mutations, these patients were associated with response to AG-120 monotherapy; 4/7 patients who achieved a response experie… (full text at CIViC) PMID 25583779 · 2015 · Open in CIViC | civic |
| IDH1 R132C + IDH1 R132H2 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID12902Popovici-Muller et al. report that IDH1 R132 mutations are gain-of-function alterations that result in production of the oncometabolite D-2-hydroxyglutarate (2-HG). The authors state that elevated 2-H… (full text at CIViC) PMID 29670690 · Popovici-Muller et al., 2018 · Open in CIViC | civic |
| Ivosidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID12903Popovici-Muller et al. reported preliminary efficacy data from an ongoing phase 1 study of ivosidenib (AG-120) monotherapy in patients with IDH1-mutated malignancies. In patients with relapsed or refr… (full text at CIViC) PMID 29670690 · Popovici-Muller et al., 2018 · Open in CIViC | civic |
| IDH1 R132H2 | ||||||||
| Ivosidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13075In a multicenter phase I dose-escalation and expansion study, 125 patients with relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) received ivosidenib 500 mg once daily. The complete rem… (full text at CIViC) PMID 29860938 · DiNardo et al., 2018 · Open in CIViC | civic |
| Olutasidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID13079In a final five-year analysis of a multicenter phase 2 trial, 35 patients with relapsed/refractory IDH1 R132H-mutated acute myeloid leukemia (AML) received olutasidenib monotherapy. The overall respo… (full text at CIViC) PMID 41239466 · Cortes et al., 2025 · Open in CIViC | civic |
| IDH1 R132L1 | ||||||||
| Ivosidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2021In a clinical study of 17 relapsed or refractory AML patients harboring IDH1 mutations, patients were associated with response to AG-120 monotherapy; 4/7 patients who achieved a response experienced c… (full text at CIViC) PMID 25583779 · 2015 · Open in CIViC | civic |
| IDH1 R132S1 | ||||||||
| Ivosidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2340In a clinical study of 17 relapsed or refractory AML patients harboring IDH1 mutations, patients were associated with response to AG-120 monotherapy; 4/7 patients who achieved a response experienced c… (full text at CIViC) PMID 25583779 · 2015 · Open in CIViC | civic |
| IDH2 Mutation5 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 3 | accepted | EID328In patients with IDH2 R140 and R172 mutation, the presence of mutation does not impact overall survival or disease free survival. PMID 20421455 · Thol et al., 2010 · Open in CIViC | civic |
| Enasidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID5069A first-in-human phase 1/2 trial assessing the pharmacology, safety and activity of Enasidenib in IDH2-mutant myeloid hematoblastosis patients. In the AML subgroup (n=176, (n=130 R140; n=45 R172; n=1 … (full text at CIViC) PMID 28588020 · Stein et al., 2017 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | ||||||
| IDH2 R1404 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | accepted | EID350In AML, patients with IDH2 R140 mutation have improved overall survival compared to those with wild-type IDH2. PMID 21596855 · Green et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 2 | accepted | EID327In this meta-analysis of adult non-promyelocytic AML (11 studies), patients with IDH2 R140 or R172 mutations had event free survival and overall survival similar to those with wild-type IDH2. PMID 22616558 · Zhou et al., 2012 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support | ||||
| IDH2 R1721 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID1511In a study of 1,540 patients with Acute Myeloid Leukemia, 18 patients had a mutation in IDH2(R172). IDH2(R172) mutations rarely showed co-mutation with NPM1 (odds ratio= 0.06; P=4x10-5), whereas IDH2… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| IDH2 R172K2 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID375In AML, patients with an IDH2 R172K mutation have worse overall survival compared to those with wild-type IDH2. PMID 21596855 · Green et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 2 | accepted | EID331AML patients with IDH2 mutations such as R172K have event free survival and overall survival similar to those with wild-type IDH2. PMID 22616558 · Zhou et al., 2012 · Open in CIViC | civic |
| JAK2 V617F4 | ||||||||
| (diagnostic) | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID5JAK2 V617F is associated with myeloid malignanices (AML, MDS, CMML/atypical CML). PMID 16081687 · Levine et al., 2005 · Open in CIViC | civic |
| 〃 | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID6JAK2 V617F is associated with myeloid neoplasms (AML, MDS, CMML/aCML). PMID 16081687 · Levine et al., 2005 · Open in CIViC | civic |
| Fedratinib | Polycythemia Vera | Predictive | D | Supports Sensitivity Response | 3 | accepted | ||
| CREBBP Fusion3 | ||||||||
| (diagnostic) | Acute Myeloid Leukemia with t(8;16)(p11.2;p13.3); KAT6A-CREBBPALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12153This is an international retrospective study by International Berlin-Frankfurt-Munster (I-BFM) AML study group including 543 pediatric AML patients from 18 countries diagnosed between 1995-2005. The a… (full text at CIViC) PMID 23974201 · Coenen et al., 2013 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with t(8;16)(p11.2;p13.3); KAT6A-CREBBPALIAS | Diagnostic | B | Supports Positive | 3 | accepted | EID12154This manuscript is the first report of a unique expression profile in pediatric AML with KAT6A::CREBBP gene fusion (known also as MOZ::CBP or MYST3::CREBBP). Genomic studies and gene expression profil… (full text at CIViC) PMID 20630590 · Serravalle et al., 2010 · Open in CIViC | civic |
| 〃 | ||||||||
| KDM6A Loss3 | ||||||||
| Olaparib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11034An array of KDM6 deficient AMP cells showed increased sensitivity to PARP inhibition. In a mouse model xenotransplant with a KDM6A loss of function AMP cell line increased susceptibility to PARP block… (full text at CIViC) | civic |
| Olaparib + VenetoclaxCombination | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11037Dual targeting of PARP (olipartinib) and BCL2 (venetoclax) was reported to be superior to either PARP or BCL2 inhibition alone in inducing primary AML cell apoptosis, and loss of KDM6A further enhance… (full text at CIViC) | civic |
| Venetoclax | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | ||||||
| RET Fusion + RET V804L1 | ||||||||
| Dasatinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Resistance | 2 | submitted | EID7515In an in vitro kinase study, the recombinant RET V804L mutant kinase demonstrated resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 101 and 91) when compared to wild typ… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| KIT D816H3 | ||||||||
| Bosutinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4153In an in vitro study, the recombinant KIT D816H mutation kinase was associated with increased sensitivity to bosutinib treatment (IC50: 32nM), as compared to wild-type KIT (IC50: 6313 nM). Sensitivit… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Dasatinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4154In an in vitro study, the recombinant KIT D816H mutation kinase was associated with increased sensitivity to dasatinib treatment(IC50: 2.6nM vs. 93.0nM), as compared to the wild-type KIT kinase. Sensi… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Imatinib Mesylate | Acute Myeloid Leukemia | |||||||
| KIT D816V9 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID26In acute myloid leukemia patients, D816 mutation is associated with earlier relapse and poorer prognosis than wildtype KIT. PMID 16384925 · Cairoli et al., 2006 · Open in CIViC | civic |
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID12410The authors studied the role of KIT D816V in acute myeloid leukemia (AML) using engineered TF-1 cells to express either wild-type KIT or KIT D816V. They discovered that KIT D816V led to constitutive a… (full text at CIViC) PMID 31311917 · Larrue et al., 2019 · Open in CIViC | civic |
| Bosutinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | ||||||
| KIT M541L1 | ||||||||
| (diagnostic) | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Diagnostic | B | Does Not Support Positive | 4 | accepted | EID485M541L mutation was not associated with CML in caucasian patients, and was common among healthy controls (8.1%), in contrast to a previous study in a Japanese CML patient population in which M541L was … (full text at CIViC) PMID 16307017 · Krüger et al., 2006 · Open in CIViC | civic |
| KIT Mutation2 | ||||||||
| Dasatinib | Core Binding Factor Acute Myeloid Leukemia | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID8576This is a prospective clinical trial testing the safety and efficacy of adding dasatinib to chemotherapy (cytarabine-daunorubicin/HiDAC) in patients with Core Binding Factor (CBF) AML (i.e RUNX1-RUNX1… (full text at CIViC) PMID 32092139 · Marcucci et al., 2020 · Open in CIViC | civic |
| Nilotinib | Acute Promyelocytic Leukemia | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID5573Compared to non-treated control cells, Kasumi-1 cells (KIT-mutated cell lines) that were exposed to nilotinib (30 uM) showed a 60% reduction in colony numbers. Further evidence to support cell death i… (full text at CIViC) PMID 28720666 · Shen et al., 2017 · Open in CIViC | civic |
| KIT N822K4 | ||||||||
| Imatinib Mesylate | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID6958Finally, although reports suggested and our study confirmed that D816 mutations were resistant to Gleevec (26), our results clearly show that t(8;21) leukemic cells carrying N822K mC-KIT, the most fre… (full text at CIViC) PMID 15650049 · Wang et al., 2005 · Open in CIViC | civic |
| Ponatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID7379In this preclinial trial, the AML cell line Kasumi-1 with c-KIT N822K mutation was treated with Ponatinib. This drug effectively inhibits both KIT phosphorylation and viability for Kasumi-1 cells at I… (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC | civic |
| Sorafenib + SunitinibSubstitutes | ||||||||
| KIT RS37335421 | ||||||||
| Selumetinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 1 | accepted | EID1136Patients with relapsed/refractory AML or 60 years old or more with untreated AML were enrolled on a phase II study of selumetinib and analyzed for mutations in KIT, NRAS, KRAS and FLT3. KIT mutation a… (full text at CIViC) PMID 24178622 · Jain et al., 2014 · Open in CIViC | civic |
Data updated 13 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.
| A |
| Supports Sensitivity Response |
| 3 |
| rejected |
EID7279In phase 1/2 trial for patients with relapsed or refractory AML with IDH2 mutation were treated with enasidenib. Overall response rate was 40.3%, with a median response duration was 5.8 months, median… (full text at CIViC) PMID 28588020 · Stein et al., 2017 · Open in CIViC |
| civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID4833Mutations in IDH1 or IDH2 are identified in approximately 20% of patients with AML.This study report the discovery and characterization of AG-221, orally available, selective, potent inhibitor of the … (full text at CIViC) PMID 28193778 · Yen et al., 2017 · Open in CIViC | civic |
| Venetoclax | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID8857In this case series, 7 elderly patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA (including 1 patient with antecedent myeloproliferative neoplasm) were t… (full text at CIViC) PMID 30725494 · Huemer et al., 2019 · Open in CIViC | civic |
| 2 |
| accepted |
EID1542In patients with acute myeloid leukemia, the presence of IDH2 R140Q (n = 7), IDH2 R172K (n = 3) or IDH1 R132 (N=4) mutations did not confer prognostic value (overall survival) compared to wild-type ID… (full text at CIViC) PMID 21997850 · Lin et al., 2012 · Open in CIViC |
| civic |
| Enasidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID10292AG-221 induces differentiation in four IDH2R140Q-mutant human AML xenograft mouse models in vivo and conferred a dose-dependent, statistically significant survival advantage in an in vivo aggressive h… (full text at CIViC) PMID 28193778 · Yen et al., 2017 · Open in CIViC | civic |
TG101348 effectively inhibits STAT5 signaling in JAK2 V617F cells.
PMID 18394554 · Wernig et al., 2008 · Open in CIViC
| civic |
| Peginterferon Alfa-2b | Polycythemia Vera | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID19In patients with JAK2 V617F, the use of pegylated IFN-alpha-2a leads to reduction in the percentage of cells harboring JAK2 V617F. PMID 16709929 · Kiladjian et al., 2006 · Open in CIViC | civic |
| Acute Myeloid Leukemia with t(8;16)(p11.2;p13.3); KAT6A-CREBBPALIAS |
| Diagnostic |
| C |
| Supports Positive |
| 3 |
| accepted |
EID12155The authors reported a congenital AML case with leukemia cutis and a cryptic insertional t(8;16)(p11.2;p13.3)/KAT6A::CREBBP fusion identified exclusively by FISH. They found KAT6A::CREBBP fusion in 11… (full text at CIViC) PMID 28097792 · Barrett et al., 2017 · Open in CIViC |
| civic |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID11036KDM6A repression was reported to sensitize AML cells to venetoclax. In addition, attenuation of KDM6 was reported to increase mitochondrial activity and intracellular ROS levels and de-reporessed BCL2… (full text at CIViC) |
| civic |
| Predictive |
| D |
| Supports Resistance |
| 3 |
| submitted |
EID6957whereas cells from a patient with t(8;21) and D816H type mC-KIT were resistant to Gleevec but sensitive to Ara-C (Fig. 4E). PMID 15650049 · Wang et al., 2005 · Open in CIViC |
| civic |
| D |
| Supports Resistance |
| — |
| submitted |
EID4161In an in vitro study, the recombinant KIT D816V mutation kinase was associated with insensitivity to bosutinib treatment (IC50: 2772nM), comparable to wild-type KIT kinase (IC50: 6313nM). Resistance w… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC |
| civic |
| Dasatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | — | submitted | EID4159In a systemic mastocytosis (SM) and acute myelogeneous leukemia (AML) patient harboring KIT D816V mutation, KIT D816V was associated with improved response to dasatinib therapy. The patient initially … (full text at CIViC) PMID 18986703 · Ustun et al., 2009 · Open in CIViC | civic |
| 〃 | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID8361In the HMC-1 human cell line, cells with KIT V560G activating mutation were treated with dasatinib and showed reduced levels of phospho-KIT, potent growth inhibition, and increased Annexin V binding a… (full text at CIViC) PMID 16434489 · Shah et al., 2006 · Open in CIViC | civic |
| 〃 | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4162In an in vitro study, the recombinant KIT D816V mutation kinase was associated with increased sensitivity to dasatinib treatment (IC50: 37nM vs. 79nM), as compared to wild-type KIT kinase. Sensitivity… (full text at CIViC) PMID 16434489 · Shah et al., 2006 · Open in CIViC | civic |
| 〃 | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4163In an in vitro study, the recombinant KIT D816V mutation kinase was associated with sensitivity to dasatinib treatment. PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Imatinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID8360In an in vitro kinase experiment, kinases wtih the KIT D816V mutation demonstrated resistance to imatinib (IC50: >10,000nM vs. 1550nM) treatment compared to the KIT wild-type kinase. In the HMC-1 huma… (full text at CIViC) PMID 16434489 · Shah et al., 2006 · Open in CIViC | civic |
| 〃 | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID8362In the HMC-1 human cell line, cells with KIT V560G activating mutation were treated with imatinib and showed reduced levels of phospho-KIT, potent growth inhibition, and increased Annexin V binding at… (full text at CIViC) PMID 16434489 · Shah et al., 2006 · Open in CIViC | civic |
| Acute Myeloid LeukemiaCURATED_BROADER |
| Predictive |
| D |
| Does Not Support Sensitivity Response |
| 3 |
| accepted |
EID7370In a preclinical trial, the AML cell line Kasumi-1 with the KIT mutation N822K was treated with the tyrosine kinase inhibitors (TKI) ponatinib, sorafenib, and sunitinib. Ponatinib was much more effect… (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC |
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| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | rejected | EID7371In a preclinical trial, Kasumi-1 AML cell lines with the KIT mutation N822K were treated with the tyrosine kinase inhibitors (TKI) ponatinib, sorafenib, and sunitinib. Ponatinib was much more effectiv… (full text at CIViC) PMID 21482694 · Gozgit et al., 2011 · Open in CIViC | civic |