Publications by authors named "Luke Ames"
AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis.
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- Acute Myeloid Leukemia (AML) results from various mutations that disrupt normal growth and differentiation of myeloid cells, leading to a dangerous increase in immature blast cells.
- Current treatments mainly involve chemotherapy, but they often fail due to the presence of dormant leukemic stem cells (LSCs) that can reactivate and cause relapse.
- This study focuses on the t(8;21) subtype of AML, revealing that LSCs in this model activate specific signaling pathways (VEGF and IL-5) that help them exit dormancy and maintain self-renewal, contributing to treatment resistance.
Article Synopsis
- Acute myeloid leukemia (AML) is a complex disease linked to various mutations, each creating its own gene regulatory network (GRN) with interacting transcription factors.
- Researchers tested the idea that important regulators for maintaining AML can be found in highly interconnected nodes of these GRNs, focusing on FLT3-ITD-mutated AML as their model.
- Their findings indicate that specific regulatory modules are essential for AML growth, and the transcription factor RUNX1 is critical, as its removal disrupts the GRN, leading to cell death.
AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting with multiple gene modules, many of which are transcription factor genes themselves. Here we hypothesized that highly connected nodes within such networks comprise crucial regulators of AML maintenance.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signaling genes. It is characterized by a disturbance of differentiation and abnormal proliferation of hematopoietic progenitors. We have previously shown that each AML subtype establishes its own core gene regulatory network (GRN), consisting of transcription factors binding to their target genes and imposing a specific gene expression pattern that is required for AML maintenance.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is associated with mutations in transcriptional and epigenetic regulator genes impairing myeloid differentiation. The t(8;21)(q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoietic master regulator RUNX1. We previously showed that the maintenance of t(8;21) AML is dependent on RUNX1-ETO expression.
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