Relapsed or refractory pediatric acute myeloid leukemia (AML) is associated with poor outcomes and relapse risk prediction approaches have not changed significantly in decades. To build a robust transcriptional risk prediction model for pediatric AML, we perform RNA-sequencing on 1503 primary diagnostic samples. While a 17 gene leukemia stem cell s...
Tumor heterogeneity poses one of the greatest challenges to a successful treatment of cancer. Tumor cell populations consist of different subpopulations that have distinct phenotypic and genotypic profiles. Such variability poses a challenge in successfully targeting all tumor subpopulations at the same time. Relapse after treatment has been previo...
10.1111/febs.16334 / FEBS Journal / 289 / 5 / 1329-1351
Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor, containing GBM stem cells (GSCs) that contribute to therapeutic resistance and relapse. Exposing potential GSC vulnerabilities may provide therapeutic strategies against GBM. Here, we interrogated the role of adenosine-to-inosine (A-to-I) RNA editing mediated by adenosi...
In this issue of JEM, Zhang et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202669) identify a dependency of glioma stem cells on tyrosine phosphatase activity of EYA2 and a new role for this phosphatase at the centrosome, offering a new therapeutic approach to target mitotic activity.
Published in Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
Background Numerous studies have shown that esophageal cancer (ESCA) contains areas of intertumoral hypoxia. It is widely accepted that the association of hypoxia with cancer stemness in the tumor microenvironment of ESCA is of profound clinical significance. However, reliable prognostic signatures based on hypoxia and cancer stemness are still lac...
BackgroundCancer metastasis is a complex process involving the spread of malignant cells from a primary tumor to distal organs. Understanding this cascade at a mechanistic level could provide critical new insights into the disease and potentially reveal new avenues for treatment. Transcriptome profiling of spontaneous cancer models is an attractive...
The commonly mutated human KRAS oncogene encodes two distinct KRAS4A and KRAS4B proteins generated by differential splicing. We demonstrate here that coordinated regulation of both isoforms through control of splicing is essential for development of Kras mutant tumors. The minor KRAS4A isoform is enriched in cancer stem-like cells, where it respond...
KAT2A is a histone acetyltransferase recently identified as a vulnerability in at least some forms of Acute Myeloid Leukemia (AML). Its loss or inhibition prompts leukemia stem cells out of self-renewal and into differentiation with ultimate exhaustion of the leukemia pool. We have recently linked the Kat2a requirement in AML to control of transcri...
PurposeA previously developed ordinary differential equation (ODE) that models the dynamic interaction and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC) was used to explain the definitive treatment failure in Glioblastoma Multiforme (GBM) for conventionally and hypo-fractionated treatments. In this ...
