The gene () has been proposed to be a proto-oncogene due to high RNA transcript levels found in multiple cancers, including myeloma, breast, lung, pancreas and esophageal cancer. The presence of an open reading frame (ORF) in humans and other primates suggests protein-coding potential. Yet, we still lack evidence of a functional MYEOV protein.
View Article and Find Full Text PDFWe present a practical guide for analyzing the genetic aspects of lymphoblastic leukaemia/lymphoma according to the 5th edition of the World Health Organization (WHO) classification of haematolymphoid neoplasms (WHO-HAEM5) issued in 2024. The WHO-HAEM5 acknowledges the increasing importance of genetics in the diagnosis of lymphoid neoplasia. Classification is based on the established genetic subtypes according to cell lineage, with precursor cell neoplasms followed by mature malignancies.
View Article and Find Full Text PDFAim: To address: What are the experiences of 2SLGBTQQIA+ parents using parenting supports and services to meet their children's early childhood development needs (<5 years of age)?
Design: Whittemore and Knafl's (2005) integrative review methodology.
Methods: Electronic databases were searched from 2000 to October 14, 2022 for empirical studies or reviews addressing the research question. The title and abstract of 12,158 articles were screened for inclusion in the review by two independent researchers; 175 of these articles underwent full-text review.
The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non-coding genome. Recent advances in epigenomic profiling have uncovered non-coding gene proximal promoters and distal enhancers of transcription genome-wide.
View Article and Find Full Text PDFChildhood B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by recurrent genetic abnormalities that drive risk-directed treatment strategies. Using current techniques, accurate detection of such aberrations can be challenging, due to the rapidly expanding list of key genetic abnormalities. Whole genome sequencing (WGS) has the potential to improve genetic testing, but requires comprehensive validation.
View Article and Find Full Text PDFIncorporating genetics into risk-stratification for treatment of childhood B-progenitor acute lymphoblastic leukaemia (B-ALL) has contributed significantly to improved survival. In about 30% B-ALL (B-other-ALL) without well-established chromosomal changes, new genetic subtypes have recently emerged, yet their true prognostic relevance largely remains unclear. We integrated next generation sequencing (NGS): whole genome sequencing (WGS) (n = 157) and bespoke targeted NGS (t-NGS) (n = 175) (overlap n = 36), with existing genetic annotation in a representative cohort of 351 B-other-ALL patients from the childhood ALL trail, UKALL2003.
View Article and Find Full Text PDFLeukemia cells re-program their microenvironment to augment blast proliferation and enhance treatment resistance. Means of clinically targeting such niche-driven treatment resistance remain ambiguous. We develop human induced pluripotent stem cell (hiPSC)-engineered niches to reveal druggable cancer-niche dependencies.
View Article and Find Full Text PDFGenomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to 3D genome structure remains poorly understood. Here, we used the highly predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogene in healthy and malignant B cells. After confirming that the model gives good predictions of Hi-C data for the nonmalignant human B cell-derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138.
View Article and Find Full Text PDFRarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin- MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data.
View Article and Find Full Text PDFChromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often called We analyzed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus () and proto-oncogene that are common in B cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterized the normal chromatin landscape of the human locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the locus of healthy B cells that was absent in samples with translocations.
View Article and Find Full Text PDFBroad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain-associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells.
View Article and Find Full Text PDFPublic Health Nutr
August 2021
Objective: While organisational change in substance use disorder (SUD) treatment has been extensively studied, there is no research describing facility-wide changes related to nutrition interventions. This study evaluates staff-perceived barriers to change before and after a wellness initiative.
Design: A pre-intervention questionnaire was administered to participating staff prior to facility-wide changes (n 40).
Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of cases of childhood precursor B-cell acute lymphoblastic leukemia. These abnormalities are too complex to engineer faithfully in animal models and are unrepresented in leukemia cell lines. As a resource for future functional and preclinical studies, we have created xenografts from the leukemic blasts of patients with intrachromosomal amplification of chromosome 21 and characterized them by and luminescent imaging, flow immunophenotyping, and histological and ultrastructural analyses of bone marrow and the central nervous system.
View Article and Find Full Text PDFBackground: The prevalence of hypertensive disorders of pregnancy (HDP) in Australia's urban indigenous women is unknown.
Aim: To explore the risk factors associated with HDP for a cohort of urban indigenous women in South-Western Sydney, Australia.
Methods: This study was conducted in partnership with the Tharawal Aboriginal Medical Service.
J Calif Dent Assoc
April 2017
Dental X-ray machine inspections are conducted by the California Department of Public Health’s Radiologic Health Branch (RHB). RHB’s mission is to protect public health and safety throughout California by ensuring the safe use of radiologic equipment and materials within industry, medicine and research, preventing radiologic health hazards and educating and enforcing applicable state and federal radiation laws and regulations.
View Article and Find Full Text PDFGenes Chromosomes Cancer
May 2017
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL.
View Article and Find Full Text PDFPublic Health Res Pract
September 2016
Risky alcohol use has significant individual health and social impacts, and is related to short- and long-term harm, including injuries, accidents, liver diseases, some cancers, cardiovascular diseases and alcohol dependence. The Get Healthy Information & Coaching Service (GHS) is a free telephone coaching service supporting adults 16 years or older to reduce weight, improve nutrition and increase physical activity. Tailored programs are available for Aboriginal people, pregnant women and people at risk of type 2 diabetes.
View Article and Find Full Text PDFPrevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.
View Article and Find Full Text PDFThe differentiation and survival of autoreactive B cells is normally limited by a variety of self-tolerance mechanisms, including clonal deletion, anergy, and clonal ignorance. The transcription factor c-ets-1 (encoded by the Ets1 gene) has B cell-intrinsic roles in regulating formation of Ab-secreting cells by controlling the activity of Blimp1 and Pax5 and may be required for B cell tolerance to self-antigen. To test this, we crossed Ets1(-/-) mice to two different transgenic models of B cell self-reactivity, the anti-hen egg lysozyme BCR transgenic strain and the AM14 rheumatoid factor transgenic strain.
View Article and Find Full Text PDFTight control of B cell differentiation into plasma cells (PCs) is critical for proper immune responses and the prevention of autoimmunity. The Ets1 transcription factor acts in B cells to prevent PC differentiation. Ets1(-/-) mice accumulate PCs and produce autoantibodies.
View Article and Find Full Text PDFIn health, long-lived plasma cells (LLPC) are essential for durable protective humoral immunity, and, conversely, in disease are a major source of pathogenic Abs in autoimmunity, graft rejection, and allergy. However, the molecular basis for their longevity is largely unknown. We have recently found that CD28 signaling in plasma cells (PC) is essential for sustaining Ab titers, by supporting the survival of LLPC, but not short-lived PC (SLPC).
View Article and Find Full Text PDFCleft Palate Craniofac J
September 2015
Objective: To determine the relationship between infant cleft size and dental arch relationship in the mixed dentition in patients with complete unilateral cleft lip and palate.
Design: Retrospective analysis of mixed longitudinal records.
Patients: A total of 29 consecutively enrolled patients with unilateral cleft lip and palate participated in a longitudinal study that included dental casts prior to lip surgery (T1: age 1 month), prior to palate surgery (T2: age 10 months), and in mixed dentition (T3: age 9 years).
Signaling through the BCR can drive B cell activation and contribute to B cell differentiation into Ab-secreting plasma cells. The positive BCR signal is counterbalanced by a number of membrane-localized inhibitory receptors that limit B cell activation and plasma cell differentiation. Deficiencies in these negative signaling pathways may cause autoantibody generation and autoimmune disease in both animal models and human patients.
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