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FLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells.

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January 2025

1Princess Margaret Cancer Centre, University Health Network; Toronto, ON M5G 1L7, Canada 14Department of Molecular Genetics, University of Toronto; Toronto, ON, Canada, Canada.

Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored towards eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FLT3 is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC, or that more potent inhibition is required, a scenario where HSC toxicity could become limiting.

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A 28-year-old woman was diagnosed with high-risk triple-expressor diffuse large B-cell lymphoma (DLBCL) (stage IV, IPI 4, CNS-IPI 5), with lymph node and extranodal involvement. The patient underwent first-line R-CHOP treatment, achieving a partial response with residual mediastinal uptake. A second-line platinum-based therapy with a transplant plan followed, resulting in stable disease; thus, she was considered refractory and started third-line therapy with CAR-T cells, receiving additional chemotherapy as bridging therapy.

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The recent severe acute respiratory syndrome coronavirus 2 pandemic has clearly exemplified the need for broad-spectrum antiviral (BSA) medications. However, previous outbreaks show that about one year after an outbreak, interest in antiviral research diminishes and the work toward an effective medication is left unfinished. Martin et al.

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