Hematologic Malignancy
Acute Leukemia
CI-CAN-00000399Explore in graph →
Hematologic1,259 active trials30 approved drugs323 evidence items
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Hematologic Malignancy
CI-CAN-00000399Explore in graph →
Variants & evidence
645 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 N841K1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 2 | submitted | EID8899The study screened for mutations in the second tyrosine kinase domain of FLT3 (TK2) in 172 untreated patient with de novo AML. Nonisotopic RNase cleavage assay was used to identify samples that did no… (full text at CIViC) PMID 15625552 · Matsuno et al., 2005 · Open in CIViC | civic |
| FLT3 N841T1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 4 | submitted | EID9237This study identified genetic driver mutations by sequencing 111 genes and cytogenetic studies in 1540 samples across three different clinical trials. The prognostic significance of FLT3 tyrosine kina… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| FLT3 Overexpression1 | ||||||||
| Sunitinib | Adult B Acute Lymphoblastic LeukemiaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1528A 25-year-old Caucasian male presented with a second relapse of B-ALL. RNA sequencing revealed FLT3 overexpression (also confirmed by IHC). The patient was treated with 22 days of sunitinib, permittin… (full text at CIViC) PMID 27181063 · Griffith et al., 2016 · Open in CIViC | civic |
| FLT3LG Expression + FLT3 OverexpressionFLT3LGFLT32 | ||||||||
| AG1295 + Crenolanib + R406Substitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID11089In some cancers such as infant ALL, B-lineage ALL and AML samples with the highest levels of wild-type FLT3, constitutive FLT3 phosphorylation is seen from paracrine or autocrine activation from FLT3 … (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
| FLT3 Tyrosine Kinase Inhibitor TTT-3002 + KW2449 + Lestaurtinib + Linifanib + Midostaurin + Ponatinib + Quizartinib + SunitinibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | ||||
| FLT3 Q575del3 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 5 | submitted | EID930246-year-old woman with normal karyotype AML; negative for ITD mutation by PCR-based FLT3 testing. Based on negative FLT3-ITD: Treated with phase 1B standard cytarabine and daunorubicin (7+3) induction… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 5 | submitted | EID930346-year-old woman with normal karyotype AML; negative for ITD mutation by PCR-based FLT3 testing. Based on negative FLT3-ITD: Treated with phase 1B standard cytarabine and daunorubicin (7+3) induction… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Lestaurtinib + Midostaurin + Sorafenib + | ||||||||
| FLT3 S574del1 | ||||||||
| Crenolanib + Lestaurtinib + Midostaurin + Ponatinib + Quizartinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9308The 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 |
| FLT3 TKD MUTATION7 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID373In AML patients, FLT3-TKD mutation was associated with poorer disease free survival compared to patients with wild type FLT3. PMID 17940205 · Whitman et al., 2008 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | accepted | EID171Event-free survival was significantly improved in patients with both NPM1 and FLT3-TKD mutations compared to patients with 1) FLT3-TKD mutations alone 2) either NPM1 or FLT3-TKD when FLT3-ITD patients… (full text at CIViC) PMID 17965322 · Bacher et al., 2008 · Open in CIViC | civic |
| (diagnostic) | Acute Myeloid LeukemiaCURATED_BROADER | Diagnostic | ||||||
| FLT3 V592_D593INSDFREY4 | ||||||||
| Palbociclib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4742In 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 | EID4739In 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 V592G1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID13031The FLT3 V592G variant was found in a patient with AML. BaF3 cells transformed to express V592G demonstrated proliferation in the absence of IL-3 similar to D835Y positive control. Cell proliferation … (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| FLT3 V592I2 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 2 | rejected | EID12964Longitudinal study analyzing blood samples over time for CHIP. The V592I was found with a VAF 0.53% (below normal CHIP threshold) in a control individual who did not develop AML. PMID 31004019 · Young et al., 2019 · Open in CIViC | civic |
| 〃 | 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 |
| 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 | |||||||
Data updated 4 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.
| 3 |
| submitted |
EID11088In some cancers such as infant ALL, B-lineage ALL and AML samples with the highest levels of wild-type FLT3, constitutive FLT3 phosphorylation is seen from paracrine or autocrine activation from FLT3 … (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC |
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| Acute Myeloid LeukemiaCURATED_BROADER |
| Predictive |
| D |
| Supports Sensitivity Response |
| 5 |
| submitted |
EID9304In this functional study: FLT-3/Q575Δ rendered transduced Ba/F3 cells (with this construct) to IL-3–independent growth (similar to FLT3 ITS and D835Y), leading to activation of downstream signaling th… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC |
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| B |
| Does Not Support Positive |
| 3 |
| accepted |
EID214WBC counts were not significantly different in AML patients with FLT3 D835 mutations compared to wild type. PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC |
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| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 3 | accepted | EID322AML patients with D835 mutation of FLT3 did not have worse overall survival than patients with wild type FLT3. PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID9246This study compares the genetic drivers identified in a relatively young population of patients with AML across three multicenter clinical trials (AML-HD98A, AML-HD98B, and AMLSG-07-04). FLT3 (both IT… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1295In a phase 2 clinical study of 95 AML/high-risk MDS patients treated with either 50 or 100 mg midostaurin, 35 harbored FLT3 mutations (26 had FLT3 ITD, 9 had FLT3 D835Y mutations). A higher percentage… (full text at CIViC) PMID 20733134 · Fischer et al., 2010 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID248Sorafenib is effective in patients with FLT3 internal tandem repeat mutations, but not in patients with wild type or D835 mutation. PMID 18230792 · Zhang et al., 2008 · Open in CIViC | civic |
| Predictive |
| C |
| Supports Sensitivity Response |
| — |
| submitted |
EID4740In 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 | EID4741In 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 |
| 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 |