Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma.

Introduction: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

Cytopenias and infections following ciltacabtagene autoleucel in heavily-pretreated relapsed or refractory multiple myeloma.

Ciltacabtagene autoleucel (cilta-cel) was FDA-approved in February 2022 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On CARTITUDE-1 trial, grade ≥3 cytopenias and infections were common. Herein, we sought to characterize cytopenias and infections after cilta-cel infusion in the standard-of-care setting.

Peripheral blood somatic mosaicism and clonal hematopoiesis across ancestry backgrounds.

Somatic mosaicism (SM), the presence of somatic mutations, is classified as clonal hematopoiesis (CH) when it occurs in hematopoietic cells at an age-related rate. CH is associated with risk for hematologic malignancies and cardiovascular disease, but most studies are predominately based on individuals of European ancestry. Using peripheral blood whole exome sequencing data from 125,748 individuals of diverse genetic ancestries, we cataloged 503,703 SM mutations based on low variant allele frequency distributions and 89,361 CH variants based on age-skewing.

Clonal Hematopoiesis in Patients With Human Immunodeficiency Virus and Cancer.

Background: Cancer-related deaths for people with human immunodeficiency virus (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH.

SHP2 inhibition displays efficacy as a monotherapy and in combination with JAK2 inhibition in preclinical models of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocytosis, and primary myelofibrosis, are clonal hematopoietic neoplasms driven by mutationally activated signaling by the JAK2 tyrosine kinase. Although JAK2 inhibitors can improve MPN patients' quality of life, they do not induce complete remission as disease-driving cells persistently survive therapy. ERK activation has been highlighted as contributing to JAK2 inhibitor persistent cell survival.

Clonal Hematopoiesis as a Molecular Risk Factor for Doxorubicin-Induced Cardiotoxicity: A Proof-of-Concept Study.

Purpose: The main dose-limiting toxicity of anthracyclines is cardiotoxicity. Clonal hematopoiesis (CH), somatic mutations in hematopoietic stem or progenitor cells in patients without hematologic malignancy, is also associated with risk for adverse cardiovascular events and worse outcomes overall. We hypothesize that CH increases risk for doxorubicin-induced cardiotoxicity (DIC).

A harmonized resource of integrated prostate cancer clinical, -omic, and signature features.

Genomic and transcriptomic data have been generated across a wide range of prostate cancer (PCa) study cohorts. These data can be used to better characterize the molecular features associated with clinical outcomes and to test hypotheses across multiple, independent patient cohorts. In addition, derived features, such as estimates of cell composition, risk scores, and androgen receptor (AR) scores, can be used to develop novel hypotheses leveraging existing multi-omic datasets.

Impact of obesity on chemotherapy dosing of carboplatin and survival of women with ovarian cancer.

Background: The study objective is to examine the impact of obesity on frontline carboplatin dosing in the neoadjuvant and adjuvant settings and to evaluate the association of dosing with survival among epithelial ovarian cancer (EOC) patients.

Methods: We selected 1527 women diagnosed with EOC from January 1, 2011 to October 20, 2021 from a nationwide electronic health record-derived de-identified database. The dose reduction of frontline carboplatin was defined as a relative dose intensity (RDI) < 0.

curatedPCaData: Integration of clinical, genomic, and signature features in a curated and harmonized prostate cancer data resource.

Genomic and transcriptomic data have been generated across a wide range of prostate cancer (PCa) study cohorts. These data can be used to better characterize the molecular features associated with clinical outcomes and to test hypotheses across multiple, independent patient cohorts. In addition, derived features, such as estimates of cell composition, risk scores, and androgen receptor (AR) scores, can be used to develop novel hypotheses leveraging existing multi-omic datasets.

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium.

Purpose: Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label.

Methods: Data were retrospectively collected from patients with RRMM who underwent leukapheresis as of February 28, 2022, at 11 US institutions with intent to receive SOC ide-cel.

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting.

Racial and ethnic differences in clonal hematopoiesis, tumor markers, and outcomes of patients with multiple myeloma.

Multiple myeloma (MM) incidence, mortality, and survival vary by race and ethnicity, but the causes of differences remain unclear. We investigated demographic, clinical, and molecular features of diverse MM patients to elucidate mechanisms driving clinical disparities. This study included 495 MM patients (self-reported Hispanic, n = 45; non-Hispanic Black, n = 52; non-Hispanic White, n = 398).

Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma.

Background: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts.

Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence.

spatialTIME and iTIME: R package and Shiny application for visualization and analysis of immunofluorescence data.

Summary: Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME.

Tank Binding Kinase 1 modulates spindle assembly checkpoint components to regulate mitosis in breast and lung cancer cells.

Error-free progression through mitosis is critical for proper cell division and accurate distribution of the genetic material. The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase regulates the progression from metaphase to anaphase and its activation is controlled by the cofactors Cdc20 and Cdh1. Additionally, genome stability is maintained by the spindle assembly checkpoint (SAC), which monitors proper attachment of chromosomes to spindle microtubules prior to cell division.