FLT3-ITD

[Blood] 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 Cancer Journal] 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.

[Signal Transduction and Targeted Therapy] 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.

[Cell Death Discovery] 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.

[Haematologica] 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] Scientists analyzed the frequency, clinical significance, and prognostic relevance of RAS pathway alterations in 328 pediatric patients with de novo acute myeloid leukemia.