Hematologic Malignancy
Acute Myeloid Leukemia
CI-CAN-00001674AML · ANLLExplore in graph →
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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 |
|---|---|---|---|---|---|---|---|---|
| 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 N/A | 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 |
| 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 |
| 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 | ||||||
| KIT D816H1 | ||||||||
| Imatinib Mesylate | Acute Myeloid LeukemiaCURATED_BROADER | 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 |
| KIT D816V3 | ||||||||
| (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 |
| Dasatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | |||||
| 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 |
| ABI1 Fusion1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9750In this study of pediatric cases of acute myeloid leukemia (AML) comparing the prognosis of several recurrent translocation partners for the KMT2A/MLL gene at 11q23, the the specific MLL-ABI1 fusion g… (full text at CIViC) PMID 19528532 · Balgobind et al., 2009 · Open in CIViC | civic |
| AFDN Fusion2 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 5 | submitted | EID9748In this study of pediatric cases of acute myeloid leukemia (AML) comparing the prognosis of several recurrent translocation partners for the KMT2A/MLL gene at 11q23, the specific MLL-AF6 fusion gene (… (full text at CIViC) PMID 19528532 · Balgobind et al., 2009 · Open in CIViC | civic |
| 〃 | Childhood Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID8515This is a large international retrospective study of the association between fusion partner and outcome in 756 children with KMT2A-rearranged (also known as MLL-rearranged) AML from 11 study group inc… (full text at CIViC) PMID 19528532 · Balgobind et al., 2009 · Open in CIViC | civic |
| KMT2A Amplification1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | E | Supports Poor Outcome | 2 | submitted | EID10071KMT2A is not a frequent finding. This study evaluate patients with this condition (n= 37 patients) detected by cytogenetics studies in the setting of AML/MDS. All patients showed a complex karyotype. … (full text at CIViC) PMID 31425921 · Sakhdari et al., 2019 · Open in CIViC | civic |
| MLLT10 Fusion1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9749In this study of pediatric cases of acute myeloid leukemia (AML) comparing the prognosis of several recurrent translocation partners for the KMT2A/MLL gene at 11q23, the specific MLL-AF10 fusion gene … (full text at CIViC) PMID 19528532 · Balgobind et al., 2009 · Open in CIViC | civic |
| MLLT3 Fusion1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | A | Supports Poor Outcome | 4 | submitted | EID8500Based on the 2016 revision to the World Health Organization classification of Myeloid Neoplasms and Acute Leukemia and in Supplemental Table 1 (PMID: 27069254), referencing Balgobind et al (PMID: 1952… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| KMT2A Fusion4 | ||||||||
| (diagnostic) | Acute Myeloid Leukemia with KMT2A RearrangementALIAS | Diagnostic | A | Supports Positive | 4 | accepted | EID1029In this publication, the 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia is discussed. The MLL-MLLT3 translocation, along with other MLL tra… (full text at CIViC) PMID 19357394 · Vardiman et al., 2009 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with KMT2A RearrangementALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12413In this 2018 study the authors include 1,023 young people diagnosed with acute myeloid leukemia (AML). The age at presentation for the participants ranged from 0 to 29 years (median of 10 years). The … (full text at CIViC) PMID 29227476 · Bolouri et al., 2018 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with KMT2A Rearrangement | |||||||
| MECOM Overexpression1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID8597Clinically, high MECOM (EVI1) expression occurs in approximately 8% of patients with de novo AML. In AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2), aberrant MECOM expression is caused by a break poin… (full text at CIViC) PMID 20308656 · Gröschel et al., 2010 · Open in CIViC | civic |
| MECOM rearrangement4 | ||||||||
| (diagnostic) | Acute Myeloid Leukemia with MECOM Rearrangement | Diagnostic | B | Supports Positive | 3 | accepted | EID12399In this study, 17 patients with a variant pericentric inv(3) were identified from an institutional cytogenetics database, out of283 myeloid neoplasms with a MECOM rearrangement (MECOM-R) confirmed b… (full text at CIViC) PMID 36672407 · Tang et al., 2023 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with MECOM Rearrangement | Diagnostic | B | Supports Positive | 3 | accepted | EID12400This study evaluates the frequency of MECOM rearrangements by fluorescence in situ hybridization (FISH) in 76 AML and 21 MDS patients with various 3q chromosomal aberrations. Patients were referred to… (full text at CIViC) PMID 26815134 · Baldazzi et al., 2016 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with MECOM Rearrangement | Diagnostic | B | |||||
| MECOM t(3;21)(q26.2;q22)1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | C | Supports Poor Outcome | 2 | submitted | EID9719t(3;21)(q26.2;q22) is a rare variant of AML, occurring in approximately 1% of cases. It carries a very poor prognosis with none of the reported patients surviving longer than 28 months and with an ave… (full text at CIViC) PMID 22706870 · Li et al., 2012 · Open in CIViC | civic |
| GATA1 Fusion1 | ||||||||
| (diagnostic) | Acute Basophilic Leukemia | Diagnostic | C | Supports Positive | 3 | submitted | EID7217Acute basophilic leukemia is a very rare subtype of acute myeloid leukemia. This study reports 4 cases of ABL with a t(X;6)(p11;q23) translocation occurring in male infants. Authors performed multiple… (full text at CIViC) PMID 21474671 · Quelen et al., 2011 · Open in CIViC | civic |
| NPM1 EXON 11 MUTATION9 | ||||||||
| (diagnostic) | Acute Myeloid LeukemiaCURATED_BROADER | Diagnostic | A | Supports Positive | 5 | accepted | EID116AML with mutated NPM1 is a provisional entity in the World Health Organization (WHO) classification of acute myeloid leukemia (AML). This mutation should be tested for in clinical trials and is recomm… (full text at CIViC) PMID 19357394 · Vardiman et al., 2009 · Open in CIViC | civic |
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 5 | accepted | EID176Complete remission rates were higher (70.5% vs 54.7%, P = 0.003) and event-free survival was longer (median, 428 vs 336 days; P = 0.012) for normal karyotype AML patients (median age 60.3 years) with … (full text at CIViC) PMID 16076867 · Schnittger et al., 2005 · Open in CIViC | civic |
| (diagnostic) | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
Data updated 7 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.
| 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 |
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| 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) |
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| 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 |
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| 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 |
| Diagnostic |
| B |
| Supports Positive |
| 4 |
| accepted |
EID12414In this 2024 study the authors included patient data from 1256 children (aged less than 19 years) across 15 different countries diagnosed with KMT2A rearranged acute myeloid leukemia (AML). KMT2A rear… (full text at CIViC) PMID 38621200 · van Weelderen et al., 2024 · Open in CIViC |
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| 〃 | Acute Myeloid Leukemia with KMT2A RearrangementALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12415In this 2023 publication the authors include 3401 KMT2A rearranged leukemia samples obtained from different diagnostic centers worldwide, and subject them to DNA sequence analyses. Of these patients, … (full text at CIViC) PMID 37019990 · Meyer et al., 2023 · Open in CIViC | civic |
| 3 |
| accepted |
EID12401In this study, samples from 33 patients presenting with AML or MDS were collected from either the Erasmus Hematology Department biobank (The Netherlands) or from the Munich Leukemia Laboratory (German… (full text at CIViC) PMID 32219447 · Ottema et al., 2020 · Open in CIViC |
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| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID13307This retrospective study from the I-BFM AML study group included 59 patients aged 0–21 years with de novo AML harboring a MECOM rearrangement (inv(3)/t(3;3) or other 3q26 rearrangements), diagnosed be… (full text at CIViC) | civic |
| Diagnostic |
| B |
| Supports Negative |
| 4 |
| accepted |
EID111NPM1 mutations were not associated with the M2 FAB subtype of acute myeloid leukemia. PMID 16076867 · Schnittger et al., 2005 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Diagnostic | B | Supports Positive | 4 | accepted | EID118NPM1 mutations were associated with M4, M5a and M5b FAB subtypes of acute myeloid leukemia. PMID 16076867 · Schnittger et al., 2005 · Open in CIViC | civic |
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID173NPM1 mutation without FLT3-ITD was associated with reduced relapse risk and increased overall survival in young adult acute myeloid leukemia patients (median age 43). PMID 17957027 · Gale et al., 2008 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID181NPM1 mutation (N=724) was associated with higher complete remission rates (92% vs 82%; P < 0.0001), lower cumulative incidence of relapse (42% vs 58%; P < 0.0001) and higher overall survival (48% vs 2… (full text at CIViC) PMID 24855211 · Linch et al., 2014 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID184NPM1 mutations were associated with increased complete remission rates as well as longer overall disease free survival in normal karyotype AML patients >59 years old, particularly in those >69 years o… (full text at CIViC) PMID 20026798 · Becker et al., 2010 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1102Peripheral blood from NPM1 mutated AMLs was assessed for NPM1 mutation status at multiple time points using RT-qPCR with primers designed to amplify different mutant NPM1 transcripts. The test develop… (full text at CIViC) PMID 26789727 · Ivey et al., 2016 · Open in CIViC | civic |
| (diagnostic) | Acute Myeloid LeukemiaCURATED_BROADER | Diagnostic | B | Supports Positive | 3 | accepted | EID119NPM1 mutations were associated with M5a and M5b FAB subtypes of acute myeloid leukemia. PMID 16455956 · Thiede et al., 2006 · Open in CIViC | civic |