Cancer Family
Bone Marrow Neoplasm
CI-CAN-00000093Explore in graph →
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Cancer Family
CI-CAN-00000093Explore 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 |
|---|---|---|---|---|---|---|---|---|
| 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 |
| KIT V560G2 | ||||||||
| Bosutinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4134In an in vitro study, the recombinant KIT V560G mutation kinase was associated with increased sensitivity to bosutinib treatment (IC50: 181nM), as compared to wild-type KIT kinase (IC50: 6313nM). Sens… (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 | EID4135In an in vitro study, the recombinant KIT V560G mutation kinase was associated with increased sensitivity to dasatinib treatment (IC50: 1.5nM vs 93.0nM), as compared to wild-type KIT kinase. Sensitivi… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| KIT V654A2 | ||||||||
| Bosutinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4149In an in vitro study, the recombinant KIT V654A mutation was associated with increased sensitivity to bosutinib treatment (IC50:132 nM), as compared to wild-type KIT kinase (IC50: 6313 nM). Sensitivi… (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 | EID4150In an in vitro study, the recombinant KIT V654A mutation was associated with increased sensitivity to dasatinib treatment (IC50: 4.2nM vs, 93.0nM), as compared to wild-type KIT kinase. Sensitivity was… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · 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 | |||||||
| KRAS Mutation1 | ||||||||
| (predisposing) | Chronic Myelomonocytic Leukemia | Predisposing | D | Supports Likely Pathogenic | 3 | submitted | EID7166Plays a causative role in leukemogenesis. RAS existed in a GTP-bound state in greater abundance than wild type, leading to increased phosphorylation of ERK (Fig. 2) Identified as oncogenic alleles in … (full text at CIViC) PMID 19075190 · Tyner et al., 2009 · Open in CIViC | civic |
| LYN OVEREXPRESSION2 | ||||||||
| Bafetinib + DasatinibSubstitutes | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Does Not Support Resistance | 3 | accepted | EID7874The BCR-ABL1 expressing imatinib-resistant cell line MYL-R overexpresses LYN, an SRC family kinase. Dasatinib showed the most potency against MYL-R compared to the non-resistant MYL cell line (IC50: 6… (full text at CIViC) PMID 18191450 · Deguchi et al., 2008 · Open in CIViC | civic |
| Nilotinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Resistance | 1 | accepted | EID7875The BCR-ABL1 expressing imatinib-resistant cell line MYL-R overexpresses LYN, an SRC family kinase. Nilotinib showed 3.1 times less potency than bafetinib (INNO-406) against MYL-R (IC50: 993.6 nM vs. … (full text at CIViC) PMID 18191450 · Deguchi et al., 2008 · Open in CIViC | civic |
| LYN Y508F2 | ||||||||
| Axitinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | — | submitted | EID4804In an in vitro study, a K562 cell line expressing LYN Y508F mutation demonstrated sensitivity to axitinib treatment, comparable to K562 cells expressing wild-type LYN or vector. Sensitivity was determ… (full text at CIViC) PMID 26912052 · Halbach et al., 2016 · Open in CIViC | civic |
| Dasatinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4805In an in vitro study, a K562 cell line expressing LYN Y508F mutation demonstrated sensitivity to dasatinib treatment, comparable to K562 cells expressing wild-type LYN or vector. Sensitivity was deter… (full text at CIViC) PMID 26912052 · Halbach et al., 2016 · Open in CIViC | civic |
| 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 |
| MPL Mutation2 | ||||||||
| (diagnostic) | Essential Thrombocythemia | Diagnostic | A | Supports Positive | 5 | submitted | EID6383Diagnostic criterion for essential thrombocytemia according to the World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues 2016. PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| (prognostic) | Primary MyelofibrosisALIAS | Prognostic | B | Supports Better Outcome | 5 | submitted | EID7464In a study of activation mutations in MPL were prognostically informative for overall survival. They occur in 4% with ET and 8% with Primary Myelofibrosis. PMID 25037629 · Tefferi et al., 2014 · Open in CIViC | civic |
| MPL S204P1 | ||||||||
| (oncogenic) | Myeloproliferative NeoplasmCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID11008Comprehensive genomic characterization was undertaken in a total of 2035 patients including 1321 patients with essential thrombocythemia, 356 with polycythemia vera, 309 with myelofibrosis, and 49 wit… (full text at CIViC) PMID 30304655 · Grinfeld et al., 2018 · Open in CIViC | civic |
| MPL W515L1 | ||||||||
| (oncogenic) | Primary MyelofibrosisALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID7221Found MPL W515L mutation in 4/45 MF patients' bone marrow but not cheek DNA. Expression of the mutated gene in cell cultures (BaF3, 3D, or UT-7 cells) resulted increased cell growth, and in mice (via … (full text at CIViC) PMID 16834459 · Pikman et al., 2006 · Open in CIViC | civic |
Data updated 10 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 |
| 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 |
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| 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 |
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| 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 |
| 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 |