Cancer Family
Malignant Bone Marrow Neoplasm
CI-CAN-00000226Explore in graph →
1,033 active trials28 approved drugs633 evidence items
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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 V592I2 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 2 | submitted | EID12965Found in whole blood of patient (ID# 4973, appendix 2) with AML, mutational profile included FLT3 V592I VAF 55%; FLT3-ITD VAF 25%, NPM1 c.863_864insCCTG VAF 25%, DNMT3A p.Arg882His VAF 43% PMID 37586297 · Hogg et al., 2023 · Open in CIViC | civic |
| 〃 | Myeloproliferative NeoplasmCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 2 | submitted | EID12966Patient 8207 (Appendix 2) with MPN and mutational profile FLT3 V592I VAF 53%; ZRSR2 p.Cys172Tyr VAF 81% and CALR c.1154_1155insTTGTC VAF 80% PMID 37586297 · Hogg et al., 2023 · Open in CIViC | civic |
| FLT3 Y572C14 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 5 | submitted | EID12785Ba/F3 cell lines engineered to express Y572C showed sustained growth in the absence of IL-3 similar to the FLT3-ITD cell line (Figure 2A). The Ba/F3 WT expressing cell line showed growth with additio… (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID13040The paper includes 1660 newly diagnosed de novo AML cases on frontline CALGB and a total of 37 point mutations and deletions were identified in the juxtamembrane domain of the FLT3 gene. Three patient… (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 Y572del8 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID12858A pBABE expression vector with wild-type FLT3 was subjected to site-directed mutagenesis to introduce single amnio acid deletions across the juxtamembrane domain then transfected into Ba/F3 cells to c… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Crenolanib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12863Ba/F3 cell lines expressing the variant FLT3 Y572del showed sensitivity to crenolanib comparable to the FLT3-ITD construct (Figure 4). PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Lestaurtinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | ||||||
| FLT3 Y589D1 | ||||||||
| (predisposing) | Acute Myeloid LeukemiaCURATED_BROADER | Predisposing | C | N/A N/A | 1 | submitted | EID8928Single 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 Y591_V592INSVDFREYE4 | ||||||||
| Palbociclib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4734In 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 | EID4731In 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 Y6931 | ||||||||
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8285With vitro proliferation assay in Ba/F3 cells, it was found that the cells bearing FLT3-ITD Y693C/N exhibited >10-fold resistance to Gilteritinib. Similar resistance was found in cells bearing FLT3-IT… (full text at CIViC) PMID 32040554 · Tarver et al., 2020 · Open in CIViC | civic |
| FLT3 Y842C7 | ||||||||
| FLT3/ABL/Aurora Kinase Inhibitor KW-2449 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID8336The authors used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI. The FLT3/ITD Y842C mutation produced high-level resistance to KW2449, sorafenib, sunitinib a… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Lestaurtinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID8339A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified Y842C. 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 Leukemia | |||||||
| FLT3 Y842H1 | ||||||||
| (predisposing) | Acute Myeloid LeukemiaCURATED_BROADER | Predisposing | C | N/A N/A | 1 | submitted | EID8929Single 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 |
| ERG Fusion3 | ||||||||
| (diagnostic) | Acute Myeloid Leukemia with FUS-ERGALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12321This study investigates the diagnostic importance of the translocation t(16;21)(p11;q22), resulting in the TLS/FUS::ERG fusion gene, in acute myeloid leukemia (AML). The authors utilized RT-PCR to det… (full text at CIViC) PMID 9242552 · Kong et al., 1997 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with FUS-ERGALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12322This international retrospective study investigates the diagnostic features of acute myeloid leukemia (AML) with the t(16;21) translocation resulting in the FUS::ERG fusion gene in pediatric patients.… (full text at CIViC) PMID 30150206 · Noort et al., 2018 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with FUS-ERG | |||||||
| GATA1 Mutation1 | ||||||||
| (diagnostic) | Myeloid Leukemia Associated with Down Syndrome | Diagnostic | A | Supports Positive | 5 | submitted | EID8511Children with Down syndrome are at increased risk to developing Transient Abnormal Myelopoiesis (TAM) and Myeloid Leukemia associated with Down Syndrome (ML-DS). GATA1, a gene that encodes an essentia… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| GATA1 p.Ser51Alafs*861 | ||||||||
| (prognostic) | Transient Abnormal MyelopoiesisALIAS | Prognostic | C | Supports Better Outcome | 2 | submitted | EID8302We report an additional case of twin-to-twin transmission of a TAM clone with identical GATA1 exon 2 mutations in monochorionic-diamniotic twin infants without constitutional T21. This case along with… (full text at CIViC) PMID 32464589 · Roseman et al., 2020 · Open in CIViC | civic |
| GATA2 Mutation1 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | submitted | EID8343GATA2 ZF1 mutations are associated with distinct clinico-biological features and predict better prognosis, different from zinc finger 1 mutations, in AML patients. ZF1 mutations were closely associate… (full text at CIViC) PMID 30190467 · Tien et al., 2018 · Open in CIViC | civic |
| IDH1 Mutation3 | ||||||||
| Ivosidenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID7278I phase 1 trial for patients with IDH1-mutated AML, patients who received ivosidenib (AG-120). The rate of complete remission was 21.6%, the over all response rate was 30.4%. PMID 29860938 · DiNardo et al., 2018 · Open in CIViC | civic |
| Azacitidine + IvosidenibCombination | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID10313Phase 3 trial of 146 patients randomized to either IDH1 inhibitor ivosidenib and azacitidine or azacitidine and placebo revealed significantly longer event-free survival in the ivosidenib-group. Patie… (full text at CIViC) PMID 35443108 · Montesinos et al., 2022 · Open in CIViC | civic |
| Venetoclax | Acute Myeloid Leukemia | |||||||
| IDH1 R1323 | ||||||||
| (prognostic) | Myelodysplastic SyndromeCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID374IDH1 R132 mutation in patients suffering from myelodysplastic syndromes is associated with worse overall survival. PMID 20494930 · Thol et al., 2010 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 3 | accepted | EID160Mutation status of IDH1 did not change event-free survival of patients with an NPM1 mutation. PMID 20805365 · Schnittger et al., 2010 · Open in CIViC | civic |
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | ||||
Data updated 2 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.
| Oncogenic |
| C |
| Supports Oncogenicity |
| 1 |
| submitted |
EID13041The paper sequenced FLT3 in 222 adult patients with AML and no known FLT3 ITD, KIT, and NRAS mutations. Nine nonsynonmyous changes were identified including one patient with the Y572C amino acid subst… (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 5 | submitted | EID12791Ba/F3 cell lines engineered to express Y572C showed sustained growth in the absence of IL-3 similar to the D835Y expressing cell line (positive control) (Figure 1A). The Ba/F3 WT expressing cell line… (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 5 | submitted | EID12795Ba/F3 cell lines engineered to express Y572C showed sustained growth in the absence of IL-3 similar to the D835Y expressing cell line (positive control) (Figure 1B). The Ba/F3 WT expressing cell line … (full text at CIViC) PMID 30651561 · Zhang et al., 2019 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID12792Ba/F3 cell lines engineered to express Y572C showed constitutive phosphorylation of FLT3 (Figure 1B) and phosphorylation of other downstream signaling molecules such as ERK1/2, AKT (Figure 2). Based o… (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID12790To assess the impact of the Y572C variant on the structural domains of the FLT3 protein, measurements of the distance between centers of mass of alpha carbon atoms in the catalytic lobes domain were t… (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| Crenolanib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 5 | submitted | EID12796Ba/F3 cell lines engineered to express Y572C showed reduced cell viability when exposed to different concentrations of crenolanib [IC50 (nm) not supplied in text] (Figure 1c and 1e). The FLT3 D835Y po… (full text at CIViC) PMID 30651561 · Zhang et al., 2019 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12794Ba/F3 cell lines engineered to express Y572C showed reduced cell viability when exposed to different concentrations of crenolanib [IC50 (nm) 0.89] (no Figure available, data presented in supplemental … (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 5 | submitted | EID12786Ba/F3 cell lines engineered to express Y572C showed reduced cell viability when exposed to different concentrations of gilteritinib (Figure 2B and supplemental table 2). The FLT3-ITD positive control … (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 5 | submitted | EID12793Ba/F3 cell lines engineered to express Y572C showed reduced cell growth when exposed to different concentrations of PKC412 (also known as midostaurin )[IC50 (nm) 2.5] (Figure 4A) when compared to a Y5… (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12787Ba/F3 cell lines engineered to express Y572C showed reduced cell viability when exposed to different concentrations of midostaurin [IC50 (nm) 0.84] (no Figure available, data presented in supplemental… (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12789EID: 12788: Ba/F3 cell lines engineered to express Y572C showed reduced cell viability when exposed to different concentrations of quizartinib [IC50 (nm) 0.06] (no Figure available, data presented in … (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12788Ba/F3 cell lines engineered to express Y572C showed reduced cell viability when exposed to different concentrations of sorafenib [IC50 (nm) 0.41] (no Figure available, data presented in supplemental t… (full text at CIViC) PMID 39806020 · Anabtawi et al., 2025 · Open in CIViC | civic |
| D |
| Supports Sensitivity Response |
| 4 |
| submitted |
EID12861Ba/F3 cell lines expressing the variant FLT3 Y572del showed sensitivity to lestaurtinib and was 5 to 10-fold more sensitive than the FLT3-ITD construct (Figure 4). PMID 33914060 · Young et al., 2021 · Open in CIViC |
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| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12859Ba/F3 cell lines expressing the variant FLT3 Y572del showed sensitivity to midostaurin and was 5 to 10-fold more sensitive than the FLT3-ITD construct. PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Crenolanib + Lestaurtinib + Midostaurin + Ponatinib + Quizartinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 5 | submitted | EID9306The 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 |
| Ponatinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12864Ba/F3 cell lines expressing the variant FLT3 Y572del showed sensitivity to ponatinib comparable to the FLT3-ITD construct (Figure 4). PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12860Ba/F3 cell lines expressing the variant FLT3 Y572del showed sensitivity to quizartinib comparable to the FLT3-ITD construct. PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12862Ba/F3 cell lines expressing the variant FLT3 Y572del showed sensitivity to sorafenib comparable to the FLT3-ITD construct (Figure 4). PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Predictive |
| C |
| Supports Sensitivity Response |
| — |
| submitted |
EID4732In 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 | EID4733In 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 Sensitivity Response |
| 3 |
| accepted |
EID8340A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified Y842C. Cytotoxicity assessed by MTT demonstrated Ba/F3 cells expressing FLT3/IT… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8934A novel mutation (FLT3 Y842C) was detected in 2 AML patients (n = 110). Ex vivo PKC412 treatment of primary blasts resulted in suppression of constitutive FLT3 and STAT-5 activation (Figure 1D). Cell … (full text at CIViC) PMID 15345593 · Kindler et al., 2005 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID8654A screen using saturation mutagenesis of FLT3/ITD followed by selection of transfected TF1 cells in FLT3 TKIs identified Y842C. 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 | 4 | accepted | EID8337The authors used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI. The FLT3/ITD Y842C mutation produced high-level resistance to KW2449, sorafenib, sunitinib a… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID8338The authors used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI. The FLT3/ITD Y842C mutation produced high-level resistance to KW2449, sorafenib, sunitinib a… (full text at CIViC) PMID 22858906 · Williams et al., 2013 · Open in CIViC | civic |
| Diagnostic |
| C |
| Supports Positive |
| 3 |
| accepted |
EID12323This study focuses on the diagnostic characteristics of pediatric patients with the t(16;21)(p11;q22)/FUS::ERG translocation using advanced molecular methods. The authors studied four cases of pediatr… (full text at CIViC) PMID 29427188 · Zerkalenkova et al., 2018 · Open in CIViC |
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| Predictive |
| C |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID8856In 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 |
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| 3 |
| submitted |
EID12900In this post hoc long-term follow-up of the phase 3 AGILE trial (NCT03173248; median follow-up 28.6 months; n=148), IDH1 R132 mutations served as the obligate driver alteration defining patient eligib… (full text at CIViC) PMID 40706052 · Montesinos et al., 2025 · Open in CIViC |
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