1q21

In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37...

BACKGROUND: Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes. METHODS: A retrospective medical records review of all patients diagnosed with PA at the Children's Hospital of Philadelphia between 2009-2023 was conducted, analyzing medical histories and genetic testing results...

Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells (PCs) in the bone marrow and recurrent cytogenetic abnormalities. The incidence of MM worldwide is on the rise. 1q21+ has been found in ~30-40% of newly diagnosed MM (NDMM) patients.1q21+ is associated with the pathophysiological mechanisms of disease progression and drug resistance in MM. In the present review, the pathogenesis and clinicopathological features of MM patients with 1q21+ were studied, the key data of 1q21+ on the prognosis of MM patients were summarized, and the clinical treatment significance of MM patients with 1q21+ was clarified, in order to provide reference for clinicians to develop treatment strategies targeting 1q21+ ...

The European-centered genome-wide association studies of schizophrenia (SCZ) may not be well applied to non-European populations. We analyzed 1,592 reported SCZ-associated genes using the public genome data and found an overall higher Asian-European differentiation on the SCZ-associated variants than at the genome-wide level. Notable examples included 15 missense variants, a regulatory variant SLC5A10 -rs1624825, and a damaging variant TSPAN18 -rs1001292. Independent local adaptations in recent 25,000 years, after the Asian-European divergence, could have contributed to such genetic differentiation, as were identified at a missense mutation LTN1 -rs57646126-A in Asians, and a non-risk allele ZSWIM6 -rs72761442-G in Europeans...

INTRODUCTION: The definition of primary plasma cell leukemia (pPCL) has been revised from ≥20% to ≥5% circulating plasma cells (CPC). However, the precise prognosis associated with CPC remains controversial. This study aimed to investigate prognostic biomarkers for myeloma patients based on CPC presence. METHODS: A comprehensive analysis was conducted on 309 consecutive patients diagnosed with either multiple myeloma or pPCL, utilizing peripheral blood smears stained with Wright-Giemsa...

Comprehensive international consensus on cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1,256 children with KMT2A-r AML aimed to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs), and secondly, to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance...

Objective: To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center. Methods: The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ(2) test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data...

Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others...

BACKGROUND: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. METHODS: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators...

OBJECTIVE: To explore the clinical characteristics of 1q21.1 microdeletion by using single nucleotide polymorphism microarrays (SNP array). METHODS: Eighteen cases of 1q21.1 microdeletion syndrome diagnosed at the Longgang District Maternal and Child Health Care Hospital of Shenzhen City from June 2017 to December 2022 were selected as the study subjects. Clinical data of the patients were collected. Results of chromosomal karyotyping and SNP assay were retrospectively analyzed...

BACKGROUND: Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified. PATIENTS: We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022...

Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of 'predictive, preventive, and personalized' periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework...

BACKGROUND: Although several transcriptome-wide association studies (TWASs) have been performed to identify genes associated with overall breast cancer (BC) risk, only a few TWAS have explored the differences in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer. Additionally, these studies were based on gene expression prediction models trained primarily in breast tissue, and they did not account for alternative splicing of genes. METHODS: In this study, we utilized two approaches to perform multi-tissue TWASs of breast cancer by ER subtype: (1) an expression-based TWAS that combined TWAS signals for each gene across multiple tissues and (2) a splicing-based TWAS that combined TWAS signals of all excised introns for each gene across tissues...

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2...

PURPOSE: Immunological regimens are an important area of research for treating multiple myeloma (MM). Plasma cells play a crucial role in immunotherapy. PATIENTS AND METHODS: In our study, we used both single-cell RNA sequencing (scRNA-seq) and bulk sequencing techniques to analyze MM patients. We analyzed each sample using gene set variation analysis (GSVA) based on immune-related gene sets. We also conducted further analyses to compare immune infiltration, clinical characteristics, and expression of immune checkpoint molecules between the H-S100A9 and L-S100A9 groups of MM patients...

INTRODUCTION: Outcomes for patients with multiple myeloma has significantly improved through the years. This is mainly related to the use of novel agents. METHODS: This is a retrospective study that reviewed presentation and outcome of 139 patients with multiple myeloma at the Windsor Essex Regional Cancer Centre from Jan. 1, 2015 to Dec. 31, 2019. Median age was 71 years and most patients had higher risk disease (65.5% either R ISS stage II or III). 30% had high risk FISH for myeloma including del...

While 1q21+ was common genetic alteration and found to have adverse effect on prognosis, the underlying genes remain unclear. Identification of related genes may provide additional help for rational intervention. The microarray dataset GSE2658 associated with MM was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were obtained, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate their functions...

OBJECTIVE: Calprotectin (CLP), S100A6, and High Mobility Group Nucleosome-Binding Protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to inve stigate the relationship of serum CLP, S100A6, and HMGN1 levels with clinical and laboratory findings in Multiple Myeloma (MM) patients and their role in the pathogenesis of MM. MATERIALS AND METHODS: We measured serum CLP, S100A6, and HMGN1 levels in 55 newly diagnosed patients and 32 healthy controls (HC)...

Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44...

RATIONALE: Nonsecretory multiple myeloma (NSMM) is a rare subtype of multiple myelom, occurring in 1% to 2% of multiple myelom and characterized by the inability of clonal plasma cells to synthesize or secrete immunoglobulins. We describe a 71-year-old male patient who began with bone pain and was referred to hospital several times, but was not properly diagnosed and effectively treated. PATIENT CONCERNS: A 71-year-old male patient visited our hematology department, complaining of lumbago for 1 year and back pain for half a year...