Case Report: Rare IKZF1 Gene Fusions Identified in Neonate with Congenital KMT2A-Rearranged Acute Lymphoblastic Leukemia

Published: 19 January 2023Chromosomal rearrangements involving the KMT2A gene occur frequently in acute lymphoblastic leukaemia (ALL). KMT2A-rearranged ALL (KMT2Ar ALL) has poor long-term survival rates and is the most common ALL subtype in infants less than 1 year of age. KMT2Ar ALL frequently occurs with additional chromosomal abnormalities including disruption of the IKZF1 gene, usually by exon deletion. Typically, KMT2Ar ALL in infants is accompanied by a limited number of cooperative le-sions. Here we report a case of aggressive infant KMT2Ar ALL harbouring additional rare IKZF1 gene fusions. Comprehensive genomic and transcriptomic analyses were performed on sequential samples. This report highlights the genomic complexity of this particular disease and describes the novel gene fusions IKZF1::TUT1 and KDM2A::IKZF1.Laura N. Eadie, Jacqueline A. Rehn, James Breen, Michael P. Osborn, Sophie Jessop, Charlotte E. J. Downes, Susan L. Heatley, Barbara J. McClure, David T. Yeung, Tamas Revesz, Benjamin Saxon and Deborah L. Whit

DUX hunting-clinical features and diagnostic challenges associated with DUX4-rearranged leukaemia

DUX4-rearrangement (DUX4r) is a recently discovered recurrent genomic lesion reported in 4-7% of childhood B cell acute lymphoblastic leukaemia (B-ALL) cases. This subtype has favourable outcomes, especially in children and adolescents treated with intensive chemotherapy. The fusion most commonly links the hypervariable IGH gene to DUX4 a gene located within the D4Z4 macrosatellite repeat on chromosome 4, with a homologous polymorphic repeat on chromosome 10. DUX4r is cryptic to most standard diagnostic techniques, and difficult to identify even with next generation sequencing assays. This review summarises the clinical features and molecular genetics of DUX4r B-ALL and proposes prospective new diagnostic methods.Jacqueline A. Rehn, Matthew J. O’Connor, Deborah L. White and David T. Yeun

Perspectives in the design of transformerless, low-noise front-ends for detectors of large capacitance and calorimeters in elementary particle physics

The achievement of adequate signal-to-noise ratios in the measurement of the energy released by ionizing particles in detectors of large capacitance such as, for instance, calorimeter cells, frequently relies upon transformer coupling between detector and preamplifier. Such a solution, however, may not be feasible if the detector is located in a strong magnetic field. This paper discusses the possibilities opened up by a recently developed field effect transistor of large gate area, whose design has been tailored to the applications in front-end preamplifiers for calorimeters and other large capacitance detectors of frequent use in elementary particle physics

Case report: Rare case of donor cell-derived T-cell acute lymphoblastic leukaemia in a female patient after receiving an allo-transplant from her male sibling

OnlinePublDonor-derived haematological neoplasms, in which recipients present with haematological malignancies that have evolved from transplant donor stem cells, have previously been described for myelodysplastic syndrome, myeloproliferative neoplasms, acute myeloid leukaemia and less often, leukaemias of lymphoid origin. Here we describe a rare and complex case of donor-derived T-cell acute lymphoblastic leukaemia with a relatively short disease latency of less than 4 years. Through genomic and in vitro analyses, we identified novel mutations in NOTCH1 as well as a novel activating mutation in STAT5B; the latter targetable with the clinically available drugs, venetoclax and ruxolitinib.Laura N. Eadie, Jacqueline A. Rehn, Caitlin E. Schutz, Susan L. Heatley, Monika M. Kutyna, Devendra K. Hiwase, Deborah L. White, David T. Yeun

Dynamic Microstructural Evolution of Graphite under Displacing Irradiation

Graphitic materials and graphite composites experience dimensional change when exposed to radiation-induced atomic displacements. This has major implications for current and future technological ranging from nuclear fission reactors to the processing of graphene-silicon hybrid devices. Dimensional change in nuclear graphites is a complex problem involving the filler, binder, porosity, cracks and atomic-level effects all interacting within the polygranular structure. An improved understanding of the atomistic mechanisms which drive dimensional change within individual graphitic crystals is required to feed into the multiscale modelling of this system. In this study, micromechanically exfoliated samples of highly oriented pyrolytic graphite have been ion irradiated and studied in situ using transmission electron microscopy (TEM) in order to gain insights into the response of single graphitic crystals to displacing radiation. Under continuous ion bombardment, a complex dynamic sequence of deformation evolves featuring several distinct stages from the inducement of strain, the creation of dislocations leading to dislocation arrays, the formation of kink band networks and localised doming of the sample. Observing these ion irradiation-induced processes using in situ TEM reveals previously unknown details of the sequence of microstructural developments and physics driving these phenomena. A mechanistic model consistent with the microstructural changes observed is presented