Mechanisms for resistance to BCMA-targeted immunotherapies in multiple myeloma.

Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined.

The impact of high-risk cytogenetic abnormalities in extramedullary multiple myeloma in the era of novel agents: insights from a multicenter study.

Purpose: This study aimed to examine the impact of high-risk cytogenetic abnormalities (HRA) on the survival outcomes of multiple myeloma patients with extramedullary disease (EMD) in the era of novel agents, utilizing the largest dataset of extramedullary multiple myeloma patients in China.

Methods: This study included a total of 371 patients with EMD, comprising 113 patients with de novo EME and 258 patients with EMB.

Results: Patients with one HRA and those with ≥ 2 HRA demonstrated significantly worse overall survival (OS) (P < 0.

Dynamics of minimal residual disease and its clinical implications in multiple myeloma: A retrospective real-life analysis.

Background: Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications.

Individualized dynamic frailty-tailored therapy (DynaFiT) in elderly patients with newly diagnosed multiple myeloma: a prospective study.

It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle.

LncRNAs-circRNAs as Rising Epigenetic Binary Superstars in Regulating Lipid Metabolic Reprogramming of Cancers.

As one of novel hallmarks of cancer, lipid metabolic reprogramming has recently been becoming fascinating and widely studied. Lipid metabolic reprogramming in cancer is shown to support carcinogenesis, progression, distal metastasis, and chemotherapy resistance by generating ATP, biosynthesizing macromolecules, and maintaining appropriate redox status. Notably, increasing evidence confirms that lipid metabolic reprogramming is under the control of dysregulated non-coding RNAs in cancer, especially lncRNAs and circRNAs.

Direct Synthesis of Benzo[]fluorenyl Thiophosphates via Tandem Cyclization of Diynols with (RO)P(O)SH.

A general and metal-free protocol for the construction of benzo[]fluorenyl thiophosphates was developed through the cascade cyclization of easily prepared diynols and (RO)P(O)SH, with water as the only byproduct. The novel transformation involved the allenyl thiophosphate as the key intermediate, followed by Schmittel-type cyclization to achieve the desired products. Notably, (RO)P(O)SH acted not only as a nucleophile but also as an acid-promoter to initiate the reaction.

Proposed risk-scoring model for estimating the prognostic impact of 1q gain in patients with newly diagnosed multiple myeloma.

1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM.

Levetiracetam alleviates cognitive decline in Alzheimer's disease animal model by ameliorating the dysfunction of the neuronal network.

Background: Patients with Alzheimer's disease (AD) have a significantly higher risk of seizures than other individuals in an age-matched population, suggesting a close association between epilepsy and AD. We aimed to examine the effects of levetiracetam (LEV)-a drug for treating seizures-on learning and memory and the neuropathological features of AD.

Methods: We crossbred APP23 mice with microtubule-associated protein tau (MAPT) transgenic mice to generate APP23/MAPT mice.

Targeting epigenetic modifiers to reprogramme macrophages in non-resolving inflammation-driven atherosclerosis.

Epigenomic and epigenetic research has been providing several new insights into a variety of diseases caused by non-resolving inflammation, including cardiovascular diseases. Atherosclerosis (AS) has long been recognized as a chronic inflammatory disease of the arterial walls, characterized by local persistent and stepwise accelerating inflammation without resolution, also known as uncontrolled inflammation. The pathogenesis of AS is driven primarily by highly plastic macrophages via their polarization to pro- or anti-inflammatory phenotypes as well as other novel subtypes recently identified by single-cell sequencing.

Dual-Targeted Therapy Circumvents Non-Genetic Drug Resistance to Targeted Therapy.

The introduction of various targeted agents into the armamentarium of cancer treatment has revolutionized the standard care of patients with cancer. However, like conventional chemotherapy, drug resistance, either preexisting (primary or intrinsic resistance) or developed following treatment (secondary or acquired resistance), remains the Achilles heel of all targeted agents with no exception, either genetic or non-genetic mechanisms. In the latter, emerging evidence supports the notion that intracellular signaling pathways for tumor cell survival act as a mutually interdependent network extensive cross-talks and feedback loops.

Diverse Epigenetic Regulations of Macrophages in Atherosclerosis.

Emerging research on epigenetics has resulted in many novel discoveries in atherosclerosis (AS), an inflammaging-associated disease characterized by chronic inflammation primarily driven by macrophages. The bulk of evidence has demonstrated the central role of epigenetic machinery in macrophage polarization to pro- (M1-like) or anti-inflammatory (M2-like) phenotype. An increasing number of epigenetic alterations and their modifiers involved in reprogramming macrophages by regulating DNA methylation or histone modifications (e.

The mechanisms and therapeutic targets of ferroptosis in cancer.

Introduction: Ferroptosis, a form of programmed cell death, is mediated primarily by lipid peroxidation via a unique iron-dependent process. The mechanisms of ferroptosis involve the metabolisms of amino acids, irons, and lipids, and the regulation of antioxidant systems. Evidence supports the roles of ferroptosis in cancer, while metabolic reprogramming (a hallmark of cancer) renders tumor cells highly vulnerable to ferroptosis and thus provides a rationale for ferroptosis-targeted therapy for cancer.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

Background: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging.

Decoding DNA methylation in epigenetics of multiple myeloma.

Dysregulation of DNA methylation in B cells has been observed during their neoplastic transformation and therefore closely associated with various B-cell malignancies including multiple myeloma (MM), a malignancy of terminally differentiated plasma cells. Emerging evidence has unveiled pronounced alterations in DNA methylation in MM, including both global and gene-specific changes that can affect genome stability and gene transcription. Moreover, dysregulated expression of DNA methylation-modifying enzymes has been related with myelomagenesis, disease progression, and poor prognosis.

Erratum: Impact of microRNA-29b on nature killer cell in T-cell acute lymphoblastic leukemia.

[This corrects the article DOI: 10.3892/ol.2019.