Publications by authors named "Natalia Martinez-Soria"
Article Synopsis
- The MLL/AF4 fusion gene is linked to a high-risk form of pro-B acute lymphoblastic leukemia, where relapses may switch the cancer type to acute myeloid leukemia, complicating treatment.
- Research shows that during these relapses, the cancer cells retain specific genetic characteristics from the original leukemia and can develop from different stages of cell development.
- Changes in chromatin accessibility and gene regulation, particularly involving the CHD4 gene, contribute to this lineage switching, suggesting that the cancer's development is driven by faulty epigenetic control.
The fusion oncogene RUNX1/RUNX1T1 encodes an aberrant transcription factor, which plays a key role in the initiation and maintenance of acute myeloid leukemia. Here we show that the RUNX1/RUNX1T1 oncogene is a regulator of alternative RNA splicing in leukemic cells. The comprehensive analysis of RUNX1/RUNX1T1-associated splicing events identifies two principal mechanisms that underlie the differential production of RNA isoforms: (i) RUNX1/RUNX1T1-mediated regulation of alternative transcription start site selection, and (ii) direct or indirect control of the expression of genes encoding splicing factors.
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- Oncogenic transcription factors like RUNX1/ETO are key drivers of acute myeloid leukemia (AML), presenting unique challenges for therapy.
- An RNAi screen revealed that Cyclin D2 (CCND2) is vital for the survival and growth of leukemia cells driven by RUNX1/ETO, as it works with AP-1 to boost CCND2 expression.
- Targeting CCND2 through knockdown or existing drugs hampers the growth of leukemia cells and their ability to thrive in a living organism, suggesting that targeting G1 CCND-CDK complexes could be an effective treatment strategy for AML related to RUNX1/ETO.
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors.
View Article and Find Full Text PDFThis unit provides information how to use short interfering RNA (siRNA) for sequence-specific gene silencing in mammalian cells. Several methods for siRNA generation and optimization, as well as recommendations for cell transfection and transduction, are presented.
View Article and Find Full Text PDFOncogenic transcription factors such as RUNX1/ETO, which is generated by the chromosomal translocation t(8;21), subvert normal blood cell development by impairing differentiation and driving malignant self-renewal. Here, we use digital footprinting and chromatin immunoprecipitation sequencing (ChIP-seq) to identify the core RUNX1/ETO-responsive transcriptional network of t(8;21) cells. We show that the transcriptional program underlying leukemic propagation is regulated by a dynamic equilibrium between RUNX1/ETO and RUNX1 complexes, which bind to identical DNA sites in a mutually exclusive fashion.
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