Gab2 Deficiency Prevents Flt3-ITD Driven Acute Myeloid Leukemia In Vivo

Utilizing a Flt3-ITD knock-in, Dnmt3a haploinsufficient mouse model, researchers demonstrated that Gab2 was essential for the development of Flt3-ITD driven acute myeloid leukemia in vivo, asGab2 deficient mice displayed prolonged survival, presented with attenuated liver and spleen pathology and reduced blast counts.
[Leukemia]
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The IL-3, IL-5, and GM-CSF Common Receptor Beta Chain Mediates Oncogenic Activity of FLT3-ITD-Positive AML

Researchers discovered that FMS-like Tyrosine Kinase 3 (FLT3)-internal tandem duplication (ITD) directly binded to CSF2RB in acute myeloid leukemia (AML) cell lines and blasts isolated from AML patients.
[Leukemia]
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Mutational Synergy during Leukemia Induction Remodels Chromatin Accessibility, Histone Modifications and Three-Dimensional DNA Topology to Alter Gene Expression

Researchers applied an integrated genomic approach to a murine allelic series that modeled the two most common mutations in acute myeloid leukemia (AML): Flt3-ITD and Npm1c, then deconvoluted the contribution of each mutation to alterations of the epigenetic landscape and genome organization.
[Nature Genetics]
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CCT245718, a Dual FLT3/Aurora a Inhibitor Overcomes D835Y-Mediated Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia Cells

The ability of CCT245718 to overcome TKD-mediated resistance was evaluated in a cell line-based model of drug resistance to Fms-like tyrosine kinase 3 (FLT3) inhibitors.
[British Journal of Cancer]
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Actin Cytoskeleton Deregulation Confers Midostaurin Resistance in FLT3-Mutant Acute Myeloid Leukemia

Midostaurin resistance was overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant acute myeloid leukemia (AML) cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication + AML.
[Communications Biology]
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Cabozantinib Promotes Erythroid Differentiation in K562 Erythroleukemia Cells through Global Changes in Gene Expression and JNK Activation

The authors reported that cabozantinib could promote differentiation in erythroid leukemia cells and found that K562 erythroid leukemia cells treated with 1 μM cabozantinib for 72 hours underwent erythroid lineage differentiation.
[Cancer Gene Therapy]
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Depalmitoylation Rewires FLT3-ITD Signaling and Exacerbates Leukemia Progression

Investigators discovered that FLT3-ITD, one of the most frequent mutations in acute myeloid leukemia, was S-palmitoylated by the ZDHHC6 palmitoyl acyltransferase. Disruption of palmitoylation redirected FLT3-ITD to the plasma membrane and rewired its downstream signaling by activating AKT and ERK pathways in addition to STAT5.
[Blood]
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The Combination of Cudc-907 and Gilteritinib Shows Promising In Vitro and In Vivo Antileukemic Activity against FLT3-Itd AML

Investigators showed that gilteritinib and CUDC-907, a dual inhibitor of PI3K and histone deacetylases, synergistically induced apoptosis in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) cell lines and primary patient samples and had striking in vivo efficacy.
[Blood Cancer Journal]
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CD52 Is a Novel Target for the Treatment of FLT3-ITD-Mutated Myeloid Leukemia

To explore alternative therapeutics to internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3), researchers established a cellular model of monoallelic FLT3ITD/WT cells using the CRISPR-Cas9 system in a human myeloid leukemia cell line.
[Cell Death Discovery]
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FLT3 Tyrosine Kinase Inhibitors Synergize with BCL-2 Inhibition to Eliminate FLT3/ITD Acute Leukemia Cells through BIM Activation

Scientists investigated the combination of FLT3 tyrosine kinase inhibitors (TKIs) with other drugs, and found that the combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary acute myeloid leukemia samples.
[Signal Transduction and Targeted Therapy]
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A Phase I/II Study of the Combination of Quizartinib with Azacitidine or Low-Dose Cytarabine for the Treatment of Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

In an open-label Phase I/II trial, patients of any age receiving first-salvage treatment for FLT3-ITD acute myeloid leukemia (AML) or age >60 years with untreated myelodysplastic syndrome or AML were treated with quizartinib plus azacitidine or low-dose cytarabine.
[Haematologica]
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