Key Points CHD4 depletion sensitizes AML cells but not normal CD34+ progenitors to genotoxic agents by relaxing chromatin and impairing DSB repair. CHD4 depletion modulates expression of AML cell genes that regulate tumor formation in vivo and colony formation in vitro.

Spontaneous Pneumothorax in the setting of coronavirus disease 19 (COVID-19) has been rarely described and is a potentially lethal complication. We report our institutional experience. Patients with confirmed COVID-19 who were admitted at 5 hospitals within the Inova health system between February 21 and May 2020 were included in the study. We identified 1619 patients, 22 patients (1.4%) developed spontaneous pneumothorax during their hospitalization without evidence of traumatic injury.

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. KEYWORDS E2F1, microRNA, PU.1, cell cycle, differentiation, lipid synthesis, myeloid cells A central problem in biology is understanding how cell division is regulated in response to developmental and environmental cues. During macrophage development, proliferating myeloid progenitor cells undergo terminal differentiation that is coordinated with reduced cell cycle progression (1). However, terminally differentiated macrophages are not necessarily permanently cell cycle arrested, as shown by evidence that epidermal Langerhans cells and brain microglia can reenter the cell cycle to self-renew (2, 3). Thus, cell cycle arrest and terminal differentiation, while normally coincident, can be independently and actively regulated. Much remains to be learned about the mechanisms by which cell-type-specific transcription factors coordinate cell cycle arrest with differentiation.

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Inherited bone marrow failure syndromes (IBMFS) are rare cancer predisposition syndromes with an especially high risk of transformation to myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). We performed a retrospective systematic review of reported MDS/AML arising in the eight most common IBMFS to determine the frequency and outcome of chromosome 7 abnormalities. We identified 738 MDS/AML cases of 4,293 individuals. Monosomy 7 or del (7q) occurred in ~17%. Greater understanding of the roles played by sequential acquisition of genetic and cytogenetic changes will provide insights into myeloid leukemogenesis and improve the surveillance and hopefully outcomes for individuals with IBMFS.

Although respiratory symptoms are the dominant features of COVID-19 infection, myocardial injury has been described in these patients. Reported cardiac manifestations of COVID-19 infection include myocarditis, arrhythmia and acute coronary syndrome including ST elevation myocardial infarction (STEMI). STEMI is a medical emergency and timely intervention is of utmost importance to prevent mortality and long-term morbidities. In this report, we present a wide spectrum of clinical presentations, management, and outcomes for five patients with COVID-19 infection and ST elevation on ECG.

Bronchoscopic biopsy results for indeterminate pulmonary nodules remain suboptimal. Electromagnetic navigation bronchoscopy (ENB) coupled with cone beam computed tomography (CBCT) for confirmation has the potential to improve diagnostic yield. We present our experience using this multimodal approach to biopsy 17 indeterminate nodules in 14 consecutive patients from April to August 2021. Demographic information, nodule characteristics, and biopsy results were recorded. Procedures were performed in a hybrid operating room equipped with a Siemens Artis Q bi-plane CBCT (Siemens, Munich, Germany). After ENB using the superDimension version 7.1 (Medtronic, Plymouth, MN, USA) to target the lesion, radial endobronchial ultrasound was used as secondary confirmation. Next, transbronchial needle aspiration was performed prior to CBCT to evaluate placement of the biopsy tool in the lesion. The average nodule size was 21.7+/−15 mm with 59% (10/17) < 2 cm in all dimensions and 35% (6/17) showing a radiographic bronchus sign. The diagnostic yield of CBCT-guided ENB was 76% (13/17). No immediate periprocedural or postprocedural complications were identified. Our experience with CBCT-guided ENB further supports the comparable efficacy and safety of this procedure compared to other mature biopsy modalities. Studies designed to optimize the lung nodule biopsy process and to determine the contributions from different procedural aspects are warranted.

The diagnosis of extrapulmonary tuberculosis in patients with end-stage renal disease can be challenging as the signs and symptoms are often non-specific. In this study, we present a case of extrapulmonary tuberculosis in an Ethiopian woman with end-stage renal disease who had subcarinal and right hilar lymphadenopathy, moderate sized right pleural effusion, hypercalcemia, and elevated parathyroid hormone–related protein in the setting of an elevated 1,25-dihydroxyvitamin D. After being started on appropriate tuberculosis treatment, patient’s parathyroid hormone–related protein level decreased and calcium level normalized. Our literature review showed that the elevation of parathyroid hormone–related protein in extrapulmonary tuberculosis has not been well studied, and it is our aim to explore the role of parathyroid hormone–related protein in extrapulmonary tuberculosis.