Publications by authors named "Moorman A"
Rearrangements involving the DUX4 gene (DUX4-r) define a subtype of paediatric and adult acute lymphoblastic leukaemia (ALL) with a favourable outcome. Currently, there is no 'standard of care' diagnostic method for their confident identification. Here, we present an open-source software tool designed to detect DUX4-r from short-read, whole-genome sequencing (WGS) data.
View Article and Find Full Text PDFAs cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition.
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- The study explores how the mammalian brain develops through the transformation of the cranial neural plate into a closed tube essential for neural structure and function.
- Single-cell RNA sequencing was employed to create a detailed gene expression map during various stages of cranial neural tube closure in mouse embryos, successfully predicting spatial gene expression patterns.
- The findings highlight the role of Sonic hedgehog (SHH) signaling in shaping different regions of the brain, revealing complex interactions between various developmental signaling pathways.
Objective: The objective of this prospective observational research project was to have dairy producers use and assess the utility of a cull cow evaluation form.
Animals: Cull dairy cows.
Procedure: Veterinarians were recruited to enrol a purposively selected group of dairy producers into a project to evaluate a cull cow evaluation form.
Objectives: In the United States, hepatitis C is the most commonly reported bloodborne infection. It is a leading cause of liver cancer and death from liver disease and imposes a substantial burden of hospitalization. We sought to describe regional differences in hepatitis C virus (HCV)-related hospitalizations during 2012 through 2019 to guide planning for hepatitis C elimination.
View Article and Find Full Text PDFThe formed hearts of vertebrates are widely different in anatomy and performance, yet their embryonic hearts are surprisingly similar. Developmental and molecular biology are making great advances in reconciling these differences by revealing an evolutionarily conserved building plan to the vertebrate heart. This suggests that perspectives from evolution may improve our understanding of the formation of the human heart.
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- Recent trials show that over 95% of kids with a specific type of leukemia called ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL) live for at least 5 years after treatment.
- Scientists looked at different drug doses and their effects on patients from various studies to see how they compare and to better understand what treatment works best.
- The results suggest that some patients could possibly receive less intensive treatment while still being treated effectively, so future research should explore the possibility of giving less medicine.
Article Synopsis
- TP53 mutations are rare in acute lymphoblastic leukemia (ALL), making the MDM2 antagonist idasanutlin a promising treatment option for most ALL cases.
- Combining idasanutlin with the BCL-x/BCL-2 inhibitor navitoclax has shown significant antileukemic effects in laboratory models, leading to a synergistic reduction in leukemia cell viability.
- These findings highlight the potential of using both drugs together in treating high-risk and relapsed ALL patients, with the combination demonstrating effectiveness at safe drug concentration levels seen in clinical trials.
T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.
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- Risk stratification is essential for treating acute lymphoblastic leukemia (ALL) and involves creating an optimal prognostic model using factors like white blood cell count and minimal residual disease (MRD).
- Using data from four national clinical trials, researchers developed the European Working Group for Adult ALL prognostic index (EWALL-PI) to assess patient risk, finding that it accurately correlated with relapse and death rates.
- The EWALL-PI risk model outperformed existing algorithms and successfully differentiated patients into standard and high-risk groups, with high-risk patients showing significantly higher rates of relapse and lower survival.
Purpose: We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant.
Methods: Data were collected for consecutive CYP (age 1-24 years) with Philadelphia chromosome-positive or Philadelphia chromosome-negative B-ALL who received Blina as first-line therapy. Blina was given as replacement for postremission intensive chemotherapy to patients with chemotherapy intolerance or resistance.
Article Synopsis
- Targeted inhibition of WEE1 using adavosertib shows promise as a novel therapy for high-risk and relapsed acute lymphoblastic leukemia (ALL), particularly in patients with TP53 mutations.
- The study tested adavosertib's effects on 27 patient samples and found significant anti-leukemic activity, disrupting the S-phase of the cell cycle even without DNA-damaging agents.
- Additionally, the combination of adavosertib with conventional chemotherapeutics, especially cytarabine, enhances the treatment's effectiveness, suggesting a viable strategy for improving outcomes in ALL patients.
Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival.
View Article and Find Full Text PDFPurpose: Historically, patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission at the end of induction (EOI) have had poor long-term survival. The goal of this study was to examine the efficacy of contemporary therapy, including allogeneic hematopoietic stem cell transplantation (HSCT) in first remission (CR1).
Methods: Induction failure (IF) was defined as the persistence of at least 5% bone marrow (BM) lymphoblasts and/or extramedullary disease after 4-6 weeks of induction chemotherapy.
The overlapping epidemics of hepatitis C virus (HCV) and HIV infection stem from underlying behaviors and health disparities among disproportionately affected populations, especially people who inject drugs (PWID). Characterizing the prevalence of HCV-HIV coinfection offers improved data to address these underlying determinants of health. We performed a literature search for articles that describe US populations, were published during 2005-2021, and summarized evidence of the prevalence of HCV infection in recent HIV clusters and outbreaks among PWID.
View Article and Find Full Text PDFBackground: Hospitalization burden related to hepatitis C virus (HCV) infection is substantial. We sought to describe temporal trends in hospitalization rates before and after release of direct-acting antiviral (DAA) agents.
Methods: We analyzed 2000-2019 data from adults aged ≥18 years in the National Inpatient Sample.
Unlabelled: Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood.
View Article and Find Full Text PDFBackground: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia.
Methods: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study.