Malignant Bone Marrow Neoplasm

The authors screened 979 acute myelogenous leukemia patients for FLT3 variants. FLT3-internal tandem duplication (FLT3-ITD) variants have been reported in 200 patients (20.4%). The study showed that h… (full text at CIViC)

PMID 12036858 · Thiede et al., 2002 · Open in CIViC

This study reports the effect of FLT3-ITD mutations on the rate of progression of MDS to AML and on a patient's overall survival. The study cohort consisted of 82 MDS patients, with paired samples ana… (full text at CIViC)

PMID 14737077 · Shih et al., 2004 · Open in CIViC

Increasing level of FLT3-ITD mutant correlated with reduced disease-free and overall survival as well as increased relapse rate.

PMID 17957027 · Gale et al., 2008 · Open in CIViC

Patients with NPM1 mutations and low (<25%, N=63), intermediate (25-50%, N=156) or high (>50%, N=66) levels of FLT3-ITD have worse overall survival (P<0.0001 for trend) and cumulative incidence of rel… (full text at CIViC)

PMID 24855211 · Linch et al., 2014 · Open in CIViC

WBC counts were higher in AML patients with internal tandem repeat of Flt3 compared to wild type.

PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC

AML patients with internal tandem repeat of FLT3 has worse overall survival than patients with wild type FLT3.

PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC

In a study of 53 APL patients treated with combination ATRA/anthracycline chemotherapy, patients with the FLT3 ITD mutation (n=10) had higher rates of relapse (30% vs. 2.5%), lower rates of remission … (full text at CIViC)

PMID 21461300 · Hong et al., 2011 · Open in CIViC

Size of the FLT3-ITD mutant duplication had no impact on overall survival or relapse rate.

PMID 17957027 · Gale et al., 2008 · Open in CIViC

In a study of 171 APL patients treated with combination ATRA/anthracycline chemotherapy, FLT3 ITD mutations (n=35) were associated with lower 3-year OS compared to the FLT3 ITD-negative group (62% vs.… (full text at CIViC)

PMID 24981688 · Lucena-Araujo et al., 2014 · Open in CIViC

Ba/F3 cells with both FLT3-ITD and TKD mutations on the same allele have more resistance to daunorubicin than cells with FLT3-ITD alone.

PMID 15626738 · Bagrintseva et al., 2005 · Open in CIViC

In a phase 3 trial comparing gilteritinib (120 mg/day) to salvage chemotherapy (SC) in adults with relapsed or refractory FLT3- mutated AML, patients were required to have FLT3 ITD or TKD (tyrosine ki… (full text at CIViC)

PMID 31665578 · Perl et al., 2019 · Open in CIViC

In vitro gilteritinib treatment of MV4-11 and MOLM-13 cells, which endogenously express FLT3-ITD, showed growth suppression based on CellTiter GLO cytotoxicity assays with IC50 values of 0.92 nM (95% … (full text at CIViC)

PMID 28516360 · Mori et al., 2017 · Open in CIViC

This study was designed to test the efficacy of FLT3 inhibitors in vitro against FLT3-ITD and other TKD variants clinically observed. IC50s were determined from immunoblots quantifying FLT3 phosphoryl… (full text at CIViC)

PMID 27908881 · Lee et al., 2017 · Open in CIViC

This study was a randomised phase 3 trial to compare sorafenib maintenance with non-maintenance post-transplantation for patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoi… (full text at CIViC)

PMID 32791048 · Xuan et al., 2020 · Open in CIViC

CEP701 was effective in reducing blast counts of 5/14 heavily pre-treated AML patients with FLT3 mutations.

PMID 14726387 · Smith et al., 2004 · Open in CIViC

In a study of 717 newly diagnosed acute myeloid leukemia patients harboring FLT3 mutations (555 FLT3-ITD, 162 FLT3-TKD), patients were randomized to receive placebo or midostaurin. Patients receiving … (full text at CIViC)

PMID 28644114 · Stone et al., 2017 · Open in CIViC

Patients in the Beat AML published dataset (n= 214 (193 primary; 21 relapse AML)) samples were studied with an ex vivo drug sensitivity screen to test whether concomitant genomic alterations alter mid… (full text at CIViC)

PMID 32754299 · Rosenberg et al., 2020 · Open in CIViC

A panel of FLT3 tyrosine kinase inhibitors was tested against Ba/F3 cells transfected with FLT3-ITD using MTT growth/survival assay. Each of the 13 TKIs inhibited proliferation of FLT3-ITD cells in a … (full text at CIViC)

PMID 28077790 · Nguyen et al., 2017 · Open in CIViC

A phase I study of pacritinib in combination with cytarabine and daunorubicin (cohort A) or with decitabine induction (cohort B) in AML patients with FLT3 mutations. A total of thirteen patients were … (full text at CIViC)

PMID 31102119 · Jeon et al., 2020 · Open in CIViC

In a preclinical trial, multiple experiments testing the effectiveness of ponatinib on the mutation FLT3-ITD in acute myeloid leukemia (AML) were conducted. Ponatinib was very effective in targeting t… (full text at CIViC)

PMID 21482694 · Gozgit et al., 2011 · Open in CIViC

Forty-seven patients with relapsed/refractory AML or 60+ years old with untreated AML were enrolled on a phase II study. In FLT3 wild-type patients, six out of 36 (17%) had a response (1 PR, 3 MR, 2 u… (full text at CIViC)

PMID 24178622 · Jain et al., 2014 · Open in CIViC

Sorafenib is effective in patients with FLT3 internal tandem repeats, but not in wild type or D835 mutation.

PMID 18230792 · Zhang et al., 2008 · Open in CIViC

13 patients with relapsed or chemo-refractory FLT3-ITD+ AML were treated with sorafenib (200-400 mg twice daily). 12 patients showed clearance or near clearance of bone marrow myeloblasts after 27 (ra… (full text at CIViC)

PMID 22368270 · Man et al., 2012 · Open in CIViC

Six children with relapsed or refractory FLT3-ITD-positive AML received initial therapy with sorafenib (alone or in combination with clofarabine and cytarabine). Four of the patients initially achiev… (full text at CIViC)

PMID 23969938 · Baker et al., 2013 · Open in CIViC

The SORMAIN trial provides evidence that an inhibition of FLT3 through sorafenib significantly reduces the risk of relapse and death after allogeneic hematopoietic stem cell transplantation for FLT3-I… (full text at CIViC)

PMID 32673171 · Burchert et al., 2020 · Open in CIViC

Ba/F3 cells with both FLT3-ITD and TKD mutations on the same allele have more resistance to the protein tyrosine kinase (PTK) inhibitor SU5614 than cells with FLT3-ITD alone or FLT3 ITD and TKD mutati… (full text at CIViC)

PMID 15626738 · Bagrintseva et al., 2005 · Open in CIViC

ATRA treatment did not effect overall survival in patients <60 years old with FLT3-ITD mutation.

PMID 19965647 · Burnett et al., 2010 · Open in CIViC

AG1296 is effective in triggering apoptosis in Ba/F3 and primary AML cells with FLT3 internal tandem repeat.

PMID 12357354 · Tse et al., 2002 · Open in CIViC

To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in … (full text at CIViC)

PMID 26438511 · Garg et al., 2015 · Open in CIViC

In this phase III, randomized trial, 371 patients with Relapsed or Refractory FLT3-Mutated AML were randomized 2:1 to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy.… (full text at CIViC)

PMID 31665578 · Perl et al., 2019 · Open in CIViC

In this phase 3 trial (ADMIRAL), 371 patients with relapsed or refractory FLT3-mutated AML (required to have FLT3 ITD or TKD D835 or I836 mutations) were randomly assigned in a 2:1 ratio to receive ei… (full text at CIViC)

PMID 31665578 · Perl et al., 2019 · Open in CIViC

In a trial with 13 patients with relapsed or refractory FLT3-ITD AML, considered unfit for further induction chemotherapy, D835Y emerged during resistance in three cases with initial sorafenib respons… (full text at CIViC)

PMID 22368270 · Man et al., 2012 · Open in CIViC

Using molecular docking simulations, the authors computationally screened a library of clinical compounds and identified KX2-391(Tirbanibulin, an SRC/tubulin dual inhibitor) to be a candidate FLT3 inh… (full text at CIViC)

PMID 34217323 · Wang et al., 2021 · Open in CIViC

FLT3-ITD positive AML cells with lower KDM6A expression showed sensitivity to olaparib.

Open in CIViC

Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC)

PMID 24619500 · Zhang et al., 2014 · Open in CIViC

Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC)

PMID 26438511 · Garg et al., 2015 · Open in CIViC

Proliferation of Ba/F3 cells with FLT3 double mutations was studied for the activity of ponatinib. Compared to control cells with native FLT3-ITD mutant (IC50: 3.0nM), cells with double mutants, FLT3-… (full text at CIViC)

PMID 23430109 · Smith et al., 2013 · Open in CIViC

Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC)

PMID 26438511 · Garg et al., 2015 · Open in CIViC

Mutations were identified by in vitro saturation mutagenesis on the background of FLT3-ITD or FLT3-ITD/F691L. Proliferation and biochemical studies showed that the FLT3-ITD D839G (IC50 =4.1μM) and FLT… (full text at CIViC)

PMID 25847190 · Smith et al., 2015 · Open in CIViC

Ningetinib inhibited Ba/F3 cells with FLT3 ITD-F691L in cell proliferation assays. FLT3-ITD-F691L cells treated with ningetinib for 6 hours demonstrated inhibition of FLT3 phosphorylation and also pho… (full text at CIViC)

PMID 38978049 · Hu et al., 2024 · Open in CIViC

Proliferation of Ba/F3 cells with FLT3 double mutations was studied for the activity of ponatinib. Compared to control cells with native FLT3-ITD mutant (IC50: 3.0nM), cells with double mutants (FLT3-… (full text at CIViC)

PMID 23430109 · Smith et al., 2013 · Open in CIViC

Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC)

PMID 24619500 · Zhang et al., 2014 · Open in CIViC

Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC)

PMID 26438511 · Garg et al., 2015 · Open in CIViC

Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafanib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC)

PMID 24619500 · Zhang et al., 2014 · Open in CIViC

Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC)

PMID 26438511 · Garg et al., 2015 · Open in CIViC

In a study looking for mechanisms of resistance within a phase 2 study using PKC412 (midostaurin), a 60 year old male with normal karyotype AML was identified with FLT3-ITD-N676K mutation. This mutati… (full text at CIViC)

PMID 16150941 · Heidel et al., 2006 · Open in CIViC

Using a saturation mutagenesis screen, resistant clones harboring N841K were identified in a Ba/F3 proliferation assay when exposed to PLX3397 on a FLT3-ITD + F691L background (Figure 3B). The N841K m… (full text at CIViC)

PMID 25847190 · Smith et al., 2015 · Open in CIViC