Double-hit

Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma...

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Cells constantly sense and respond to not only biochemical but also biomechanical changes in their microenvironment, demanding for dynamic metabolic adaptation. ECM stiffening is a hallmark of cancer aggressiveness, while survival under substrate detachment also associates with poor prognosis. Mechanisms underlying this, non-linear mechano-response of tumor cells may reveal potential double-hit targets for cancers. Here, an integrin-GSK3β-FTO-mTOR axis is reported, that can integrate stiffness sensing to ensure both the growth advantage endowed by rigid substrate and cell death resistance under matrix detachment...

BACKGROUND: Intracerebral hemorrhage (ICH) carries significant morbidity and mortality. Previous single-center retrospective analysis suggests that end-stage renal disease (ESRD) is a risk factor for severe ICH and worse outcomes. This investigation aims to examine the impact of ESRD on ICH severity, complications, and outcomes using a multicenter national database. METHODS: The International Classification of Disease, Ninth and Tenth Revision Clinical Modification codes were used to query the National Inpatient Sample for patients with ICH and ESRD between 2010 and 2019...

Uterine leiomyomas (ULs) are non-cancerous tumors composed of smooth muscle cells that develop within the myometrium and represent the most prevalent pathological condition affecting the female genital tract. Despite the volume of available research, many aspects of ULs remain unresolved, making it a "paradoxical disease" where the increase in available scientific literature has not been matched by an increase in solid evidence for clinical management. Fertility stands at the top of the list of clinical issues where the role of ULs is still unclear...

Adverse influences during pregnancy are associated with a range of unfavorable outcomes for the developing offspring. Maternal psychosocial stress, exposure to infections and nutritional imbalances are known risk factors for neurodevelopmental derangements and according psychiatric and neurological manifestations later in offspring life. In this context, the maternal immune activation (MIA) model has been extensively used in preclinical research to study how stimulation of the maternal immune system during gestation derails the tightly coordinated sequence of fetal neurodevelopment...

Deep learning applications are emerging as promising new tools that can support the diagnosis and classification of different cancer types. While such solutions hold great potential for hematological malignancies, there have been limited studies describing the use of such applications in this field. The rapid diagnosis of double/triple-hit lymphomas (DHLs/THLs) involving MYC , BCL2 and/or BCL6 rearrangements is obligatory for optimal patient care. Here, we present a novel deep learning tool for diagnosing DHLs/THLs directly from scanned images of biopsy slides...

Nearly a billion people worldwide are infected with the hepatitis B Virus (HBV) and about a third of them have chronic infection. HBV is an important cause of morbidity and mortality, including acute and chronic hepatitis and hepatocellular carcinoma (HCC). Screening and control of primary HBV infection through vaccination represent a major advance in global public health, but large sections of the world population, in both developed and underdeveloped countries, remain unscreened and unvaccinated. In addition to being a global cause of liver disease, an important role of HBV in lymphoma has also emerged...

BACKGROUND: IMPDH2 is the rate-limiting enzyme of the de novo GTP synthesis pathway and has a key role in tumors; however, the specific mechanism underlying IMPDH2 activity in diffuse large B cell lymphoma (DLBCL) is still undetermined. This study aims to explore the potential mechanism of IMPDH2 in DLBCL, and its possible involvement in double-hit lymphoma (DHL), i.e., cases with translocations involving MYC and BCL2 and/or BCL6. METHODS: Using single-cell sequencing and bioinformatics analysis to screen for IMPDH2...

Double-hit lymphoma (DH-DLBCL) is an aggressive, and often refractory, type of B-cell non-Hodgkin lymphoma (NHL) characterized by rearrangements in MYC and BCL2. Cyclin-dependent kinase 9 (CDK9) regulates transcriptional elongation and activation of transcription factors, including MYC, making it a potential targeted approach for the treatment of MYC+ lymphomas. Enitociclib is a well-tolerated and clinically active CDK9 inhibitor leading to complete metabolic remissions in 2/7 DH-DLBCL patients treated with once weekly (QW) 30 mg intravenous administration (i...

VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly defined illness that bridges hematology, oncology, and rheumatology. Its pathophysiology originates in a mutation in the UBA1 gene that leads to a defect in ubiquitination resulting in a severe systemic inflammatory syndrome. It is associated with significant morbidity and mortality; however, data are scarce due to limited cases described in the literature. Here we describe a case of a male in his 60s who was referred to hematology-oncology due to progressive dyspnea, poor oral intake, and weight loss...

Relapsed or refractory (R/R) large B cell lymphoma (LBCL) presenting as secondary central nervous system lymphoma (SCNSL) carries a poor prognosis, with a median survival time of two to five months. Chimeric antigen receptor (CAR)-T cell therapy has been approved in R/R LBCL, but studies are ongoing to understand its efficacy and safety for SCNSL. Axicabtagene ciloleucel or tisagenlecleucel have been shown to attain high response rates in some retrospective studies; however, response durability continues to be unclear...

The utility of CD19-targeted chimeric antigen receptor T-cell (CAR-T cell) therapy in the management of refractory/relapsed B-cell malignancies has increased tremendously in recent times. In addition to cytokine release syndrome (CRS), neurotoxicity, and infections, CAR-T cell patients develop cytopenias, with about 15% of the patients continuing to have severe cytopenias up to three months after treatment. Retrospective reviews have reported the development of myelodysplastic syndrome (MDS) in patients undergoing CAR-T cell therapy...

To clarify the role of gut mucosal immunity in ASD, we evaluated, in the early-life immune activation (EIA) mouse model, the effects of administration of a monoclonal antibody directed against the integrin alpha4 beta7 (α4β7 mAb), blocking the leukocyte homing into the gut mucosa. EIA is a double-hit variant of the maternal immune-activation (MIA) model, including both prenatal (Poly I: C) and postnatal (LPS) immune challenges. In C57BL6/J EIA male adult offspring mice, IL-1β and IL-17A mRNA colonic tissue content increased when compared with controls...

PURPOSE/OBJECTIVE(S): Efficacy of dose fractionation is dependent on tumor radiosensitivity. However, due to intra-tumoral dose response heterogeneity, the advantage of fractionation cannot be fully utilized. FDG-PET/CT has been used to assess intra-tumoral dose response during the treatment course. Thus, radiosensitivity of different sub-volumes within the individual tumors can be assessed and used to design dose fractionation. MATERIALS/METHODS: For each patient, the pre-treatment FDG-PET/CT and a feedback FDG-PET/CT obtained within the 3rd week of the chemo-radiotherapy for HN cancer were used to construct tumor voxel dose response matrix, DRM...

PURPOSE/OBJECTIVE(S): There is limited data regarding the results of treating transformed Diffuse Large B-Cell Lymphoma, including the influence of radiation therapy on their overall prognosis. Thus, we aimed to investigate the clinical outcomes of transformed DLBCL patients treated at a single institution. MATERIALS/METHODS: We reviewed clinical features and outcomes of 27 patients with biopsy confirmed transformed Diffuse Large B-cell Lymphoma (DLBCL) treated at a single institution from 2005 and 2014...

PURPOSE/OBJECTIVE(S): The role of radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) is unclear. In patients treated with upfront chemotherapy for DLBCL, indications for RT are often considered to be bulky (7.5 cm +) or extranodal disease. This is thought to improve outcomes through improvement in local control. Many trials call into question the actual benefit of RT. Alliance/CALGB 50303 was a randomized phase III trial comparing two chemotherapy regimens for the treatment for DLBCL in which no patients were to receive RT...

PURPOSE/OBJECTIVE(S): Palliative radiotherapy (RT) is employed for patients with multiple myeloma to improve or prevent symptoms. However, the optimal dose fractionation is not well defined. The role of cytogenetics in informing RT warrants further study. We performed an institutional analysis of patients with multiple myeloma receiving palliative RT and assessed factors associated with local progression, with a focus on dose fractionation and cytogenetic abnormalities. MATERIALS/METHODS: We queried a prospectively maintained, departmental database for consecutive patients who received palliative RT for multiple myeloma at our institution from 2015 to 2020...

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AQP4-IgG NMOSD (anti-aquaporin-4 neuromyelitis optica spectrum disorder) and MOGAD (myelin oligodendrocyte glycoprotein antibody associated disease) are unique disorders among themselves, with rare reports of dual seropositivity being described. Evaluation with cell-based assays reduces the incidence of false positivity. The clinical features of these cases may either have a dominant phenotype or may evolve into one subsequently. We describe a young girl aged 18-year-old who presented with longitudinally extensive transverse myelitis and dual seropositivity to both AQP4 and MOG antibodies...