Medical Specialties Commons^™

Inhibition Of The Interaction Between Hippo/Yap And Akt Signaling With Ursolic Acid And 3’3-Diindolylmethane Suppresses Esophageal Cancer Tumorigenesis, Ruo Yu Meng, Cong Shan Li, Dan Hu, Soon-Gu Kwon, Hua Jin, Ok Hee Chai, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of …

Adagrasib In Advanced Solid Tumors Harboring A Krasg12c Mutation, Tanios S Bekaii-Saab, Rona Yaeger, Alexander I Spira, Meredith S Pelster, Joshua K Sabari, Navid Hafez, Minal Barve, Karen Velastegui, Xiaohong Yan, Aditya Shetty, Hirak Der-Torossian, Shubham Pant

Faculty, Staff and Student Publications

Purpose: Adagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.

Methods: In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response …

Interstitial Lung Abnormalities After Hospitalization For Covid-19 In Patients With Cancer: A Prospective Cohort Study, Sungryong Noh, Christopher Bertini, Isabel Mira-Avendano, Maryam Kaous, Bela Patel, Saadia A Faiz, Vickie R Shannon, Diwakar D Balachandran, Lara Bashoura, Roberto Adachi, Scott E Evans, Burton Dickey, Carol Wu, Girish S Shroff, Joanna-Grace Manzano, Bruno Granwehr, Shannon Holloway, Kodwo Dickson, Alyssa Mohammed, Mayoora Muthu, Hui Song, Caroline Chung, Jia Wu, Lyndon Lee, Ying Jiang, Fareed Khawaja, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients.

METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and …

Hybrid Management Of Type B Aortic Dissection In A Patient With Right-Sided Aortic Arch And Aberrant Left Subclavian Artery, Regina Husman, Madiha Hassan, Anthony L Estrera, Rana O Afifi

Faculty, Staff and Student Publications

This report describes a patient with a right-sided aortic arch, aberrant left subclavian artery and Kommerell diverticulum, who presented with aneurysmal degeneration of the aortic root to the descending aorta, in addition to an acute type B2-10 aortic dissection. He underwent hybrid treatment with a valve-sparing aortic root replacement, transverse arch replacement with reattachment of the right subclavian artery, bilateral common carotid arteries, and thoracic endovascular aneurysm repair with left subclavian artery embolization and a left common carotid to subclavian artery bypass.

Gore Ctag Sleeve-Associated Maldeployment For Traumatic Aortic Injury With Aberrant Right Subclavian Artery, Samuel Leonard, Brett Vernier, Kourosh Keyhani, Arash Keyhani, Akiko Tanaka, S Keisin Wang

Faculty, Staff and Student Publications

A 30-year-old woman presented following a motor vehicle collision with a grade III blunt thoracic aortic injury and an aberrant right subclavian artery. Using intraoperative ultrasound and diagnostic subtraction angiography, we deployed an aortic endograft (cTAG; W.L. Gore & Associates), excluding the injury and aberrant right subclavian artery. The patient immediately lost arterial waveforms in her left arm, confirming incidental coverage of the left subclavian artery, likely due to the polytetrafluoroethylene sheath of the endograft. Her pulses returned after placement of a left subclavian chimney via retrograde brachial artery access.

Open Repair Of An Infected Abdominal Aortic Aneurysm In A Patient With Vascular Ehlers-Danlos Syndrome, Bernardo C Mendes, Diego V S Rodrigues, Indrani Sen, Juan Bowen, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.

Perioperative Team-Based Morbidity And Mortality Conferences: A Systematic Review Of The Literature, Aubrey Samost-Williams, Roni Rosen, Alexander Hannenberg, Melis Lydston, Garrett M Nash, Mary Brindle

Faculty, Staff and Student Publications

OBJECTIVE: This systematic review aimed to identify key elements of perioperative team-based morbidity and mortality conferences (TBMMs) and their impact on patient safety, education, and quality improvement outcomes.

BACKGROUND: Patient safety in the perioperative period is influenced by system, team, and individual behaviors. However, despite this recognition, single-discipline morbidity and mortality conferences remain a mainstay of educational and quality improvement efforts.

METHODS: A structured search was conducted in MEDLINE Complete, Embase, Web of Science, ClinicalTrials.gov, Cochrane CENTRAL, and ProQuest Dissertations and Theses Global in July 2022. Search results were screened, and the articles meeting inclusion criteria were abstracted.

RESULTS: Seven …

Understanding Ip3r Channels: From Structural Underpinnings To Ligand-Dependent Conformational Landscape, Mariah R Baker, Guizhen Fan, Vikas Arige, David I Yule, Irina I Serysheva

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed large-conductance Ca2+-permeable channels predominantly localized to the endoplasmic reticulum (ER) membranes of virtually all eukaryotic cell types. IP3Rs work as Ca2+ signaling hubs through which diverse extracellular stimuli and intracellular inputs are processed and then integrated to result in delivery of Ca2+ from the ER lumen to generate cytosolic Ca2+ signals with precise temporal and spatial properties. IP3R-mediated Ca2+ signals control a vast repertoire of cellular functions ranging from gene transcription and secretion to the more enigmatic brain activities such as learning and memory. IP3Rs open and release Ca2+ when they bind both …

Zranb1 Is An Nbs1 Deubiquitinase And A Potential Target To Overcome Radioresistance And Parp Inhibitor Resistance In Triple-Negative Breast Cancer, Ying Mei, Qinglei Hang, Hongqi Teng, Fan Yao, Mei-Kuang Chen, Mien-Chie Hung, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

No abstract provided.

Differentiating Urgent From Elective Cases Matters In Minority Populations: Developing An Ordinal "Desirability Of Outcome Ranking" To Increase Granularity And Sensitivity Of Surgical Outcomes Assessment, Michael A Jacobs, Susanne Schmidt, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Chen-Pin Wang, Laura S Manuel, Paula K Shireman

Faculty, Staff and Student Publications

BACKGROUND: Surgical analyses often focus on single or binary outcomes; we developed an ordinal Desirability of Outcome Ranking (DOOR) for surgery to increase granularity and sensitivity of surgical outcome assessments. Many studies also combine elective and urgent procedures for risk adjustment. We used DOOR to examine complex associations of race/ethnicity and presentation acuity.

STUDY DESIGN: NSQIP (2013 to 2019) cohort study assessing DOOR outcomes across race/ethnicity groups risk-adjusted for frailty, operative stress, preoperative acute serious conditions, and elective, urgent, and emergent cases.

RESULTS: The cohort included 1,597,199 elective, 340,350 urgent, and 185,073 emergent cases with patient mean age of 60.0 …

Inorganic Fertilizer Use And Its Association With Rice Yield Gaps In Sub-Saharan Africa, Jean-Martial Johnson, Ali Ibrahim, Elliott Ronald Dossou-Yovo, Kalimuthu Senthilkumar, Yasuhiro Tsujimoto, Hidetoshi Asai, Kazuki Saito

Faculty, Staff and Student Publications

Where and which countries should receive higher priority for improving inorganic fertilizer use in rice fields in sub-Saharan Africa (SSA)? This study addressed this question by assessing the spatial variation in fertilizer use and its association with rice yield and yield gap in 24 SSA countries through a systematic literature review of peer-reviewed papers, theses, and grey literature published between 1995 and 2021. The results showed a large variation in N, P, and K fertilizer application rates and rice yield and an opportunity for narrowing the yield gap by increasing N and P rates, especially in irrigated rice systems. We …

Low Pitch Significantly Reduces Helical Artifacts In Abdominal Ct, Moiz Ahmad, Peng Sun, Christine B Peterson, Marcus R Anderson, Xinming Liu, Ajaykumar C Morani, Corey T Jensen

Faculty, Staff and Student Publications

Purpose: High helical pitch scanning minimizes scan times in CT imaging, and thus also minimizes motion artifact and mis-synchronization with contrast bolus. However, high pitch produces helical artifacts that may adversely affect diagnostic image quality. This study aims to determine the severity and incidence of helical artifacts in abdominal CT imaging and their relation to the helical pitch scan parameter.

Methods: To obtain a dataset with varying pitch values, we used CT exam data both internal and external to our center. A cohort of 59 consecutive adult patients receiving an abdomen CT examination at our center with an accompanying prior …

Rare Variants In Ano1, Encoding A Calcium-Activated Chloride Channel, Predispose To Moyamoya Disease, Amélie Pinard, Wenlei Ye, Stuart M Fraser, Jill A Rosenfeld, Pavel Pichurin, Scott E Hickey, Dongchuan Guo, Alana C Cecchi, Maura L Boerio, Stéphanie Guey, Chaker Aloui, Kwanghyuk Lee, Markus Kraemer, Saleh Omar Alyemni, Michael J Bamshad, Deborah A Nickerson, Elisabeth Tournier-Lasserve, Shozeb Haider, Sheng Chih Jin, Edward R Smith, Kristopher T Kahle, Lily Yeh Jan, Mu He, Dianna M Milewicz

Faculty, Staff and Student Publications

Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses …

Temporal Characterization Of Acute Pain And Toxicity Kinetics During Radiation Therapy For Head And Neck Cancer A Retrospective Study, Vivian Salama, Sara Youssef, Tianlin Xu, Kareem A Wahid, Jaime Chen, Jillian Rigert, Anna Lee, Katherine A Hutcheson, Brandon Gunn, Jack Phan, Adam S Garden, Steven J Frank, William Morrison, Jay P Reddy, Michael T Spiotto, Mohamed A Naser, Cem Dede, Renjie He, Abdallah S R Mohamed, Lisanne V Van Dijk, Ruitao Lin, Carlos J Roldan, David I Rosenthal, Clifton D Fuller, Amy C Moreno, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

OBJECTIVES: Pain during Radiation Therapy (RT) for oral cavity/oropharyngeal cancer (OC/OPC) is a clinical challenge due to its multifactorial etiology and variable management. The objective of this study was to define complex pain profiles through temporal characterization of pain descriptors, physiologic state, and RT-induced toxicities for pain trajectories understanding.

MATERIALS AND METHODS: Using an electronic health record registry, 351 OC/OPC patients treated with RT from 2013 to 2021 were included. Weekly numeric scale pain scores, pain descriptors, vital signs, physician-reported toxicities, and analgesics were analyzed using linear mixed effect models and Spearman's correlation. Area under the pain curve (AUC

RESULTS: …

Stromal-Derived Nrg1 Enables Oncogenic Kras Bypass In Pancreas Cancer, Jincheng Han, Jiaqian Xu, Yonghong Liu, Shaoheng Liang, Kyle A Labella, Deepavali Chakravarti, Denise J Spring, Yan Xia, Ronald A Depinho

Faculty, Staff and Student Publications

Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported. Genetic extinction or pharmacological inhibition of KRAS* resulted in up-regulation of ERBB2 and ERBB3 expression in human and murine models, which prompted cancer cell utilization of CAF-derived NRG1 as a …

Atopic Dermatitis And The Risk Of Myocardial Infarction And All-Cause Mortality: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee

Faculty, Staff and Student Publications

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various comorbidities. However, inconsistent results on the risk of myocardial infarction (MI) and mortality have been reported in patients with AD. This study was aimed to evaluate the risk of MI and all-cause mortality in patients with AD.

METHODS: This nationwide population-based retrospective cohort study enrolled 56,205 adults ≥ 20 years of age with AD and 3,825,609 controls without AD from the Korean National Health Service (NHIS) database from 2009 to 2016.

RESULTS: The risk of MI (adjusted hazard ratio [aHR], 1.111, 95% confidence interval [CI], 1.050-1.176) was …

Diversity, Equity, And Inclusion In The Melanoma Research Community, Marie E Portuallo, David Y Lu, Gretchen M Alicea, Joel Bolling, Rebecca Lee, Jennifer Mcquade, Allison Betof Warner, Michael Davies, Ashani Weeraratna, Jessie Villanueva, Vito W Rebecca

Faculty, Staff and Student Publications

The inaugural Diversity and Inclusion in Science Session was held during the 2021 Society for Melanoma Research (SMR) congress. The goal of the session was to discuss diversity, equity, and inclusion in the melanoma research community and strategies to promote the advancement of underrepresented melanoma researchers. An international survey was conducted to assess the diversity, equity, and inclusion (DEI) climate among researchers and clinicians within the Society for Melanoma Research (SMR). The findings suggest there are feelings and experiences of inequity, bias, and harassment within the melanoma community that correlate with one's gender, ethnic/racial group, and/or geographic location. Notably, significant …

The Effects Of Equine-Assisted Activities On Execution Function In Children Aged 7–8 Years: A Randomized Controlled Trial, Xiaodong Cheng, Kexin Zhen, Yongzhao Fan, Qian Tang, Hao Wu

Faculty, Staff and Student Publications

BACKGROUND: This study examines the effects of equine-assisted activity (EAA) training on executive functioning (EF) (inhibitory control, working memory, and cognitive flexibility) in children aged 7-8 years.

METHODS: Twenty-Four healthy children aged 7-8 years with a 1:1 ratio of boys to girls were randomly divided into EAA group (EAAG) or control group (CG). The subjects in EAAG were trained for 12 weeks, and CG participated in normal daily activities. All subjects conducted the Flanker, 1-Back, and More-odd shifting tasks at rest and recorded the average reaction times (RTs) and accuracy data of each task.

RESULTS: After 12 weeks of EAA …

Outcomes Of Transcatheter Aortic Valve Replacement In Patients With Cardiogenic Shock, Kashish Goel, Pinak Shah, Brandon M Jones, Ethan Korngold, Anju Bhardwaj, Biswajit Kar, Colin Barker, Molly Szerlip, Richard Smalling, Abhijeet Dhoble

Faculty, Staff and Student Publications

AIMS: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed.

METHODS AND RESULTS: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 …

Safety, Efficacy, And Pk/Pd Of Vorasidenib In Previously Treated Patients With Midh1/2 Hematologic Malignancies: A Phase 1 Study, Courtney D Dinardo, Stéphane De Botton, Daniel A Pollyea, Richard M Stone, Jessica K Altman, Amir T Fathi, Tharin Limsakun, Min Liang, Sung Choe, Mohammad Hossain, Adriana E Tron, Qian Meng, Stephanie M Kapsalis, Shuchi S Pandya, Eytan M Stein

Faculty, Staff and Student Publications

No abstract provided.

Obesity And Renal Cell Carcinoma: Biological Mechanisms And Perspectives, Neha Venkatesh, Alberto Martini, Jennifer L Mcquade, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Obesity, defined by body mass index (BMI), is an established risk factor for specific renal cell carcinoma (RCC) subtypes such as clear cell RCC, the most common RCC histology. Many studies have identified an association between obesity and improved survival after diagnosis of RCC, a potential "obesity paradox." Clinically, there is uncertainty whether improved outcomes observed after diagnosis are driven by stage, type of treatment received, or artifacts of longitudinal changes in weight and body composition. The biological mechanisms underlying obesity's influence on RCC are not fully established, but multiomic and mechanistic studies suggest an impact on tumor metabolism, particularly …

To Produce Or Not To Produce? Contrasting The Effect Of Substance Abuse In Social Decision-Making Situations, Laurent Avila-Chauvet, Diana Mejía Cruz, Óscar García-Leal, Bruno Kluwe-Schiavon

Faculty, Staff and Student Publications

Substance use disorders (SUD) have been related to high criminal justice costs, expensive healthcare, social impairment, and decision-making deficits. In non-social decision-making tasks, people with SUD tend to take more risks and choose small immediate rewards than controls. However, few studies have explored how people with SUD behave in social decision-making situations where the resources and profits depend directly on participants' real-time interaction, i.e., social foraging situations. To fulfill this gap, we developed a real-time interaction task to (a) compare the proportion of producers (individuals who tend to search for food sources) and scroungers (individuals who tend to steal or …

Activation Of Cell-Free Mtdna-Tlr9 Signaling Mediates Chronic Stress-Induced Social Behavior Deficits, Ashutosh Tripathi, Alona Bartosh, Carl Whitehead, Anilkumar Pillai

Faculty, Staff and Student Publications

Inflammation and social behavior deficits are associated with a number of neuropsychiatric disorders. Chronic stress, a major risk factor for depression and other mental health conditions is known to increase inflammatory responses and social behavior impairments. Disturbances in mitochondria function have been found in chronic stress conditions, however the mechanisms that link mitochondrial dysfunction to stress-induced social behavior deficits are not well understood. In this study, we found that chronic restraint stress (RS) induces significant increases in serum cell-free mitochondrial DNA (cf-mtDNA) levels in mice, and systemic Deoxyribonuclease I (DNase I) treatment attenuated RS-induced social behavioral deficits. Our findings revealed …

Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation And Immune Evasion, Kyung-Pil Ko, Yuanjian Huang, Shengzhe Zhang, Gengyi Zou, Bongjun Kim, Jie Zhang, Sohee Jun, Cecilia Martin, Karen J Dunbar, Gizem Efe, Anil K Rustgi, Hiroshi Nakagawa, Jae-Il Park

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Despite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown.

METHODS: Using CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing. Tumorigenicity and immune evasion of organoids were monitored by allograft transplantation. Human ESCC single-cell RNA sequencing data sets were analyzed to classify patients and find subsets relevant to organoid models and immune evasion.

RESULTS: We …

Individual Differences In Late Positive Potential Amplitude And Theta Power Predict Cue-Induced Eating, Kyla D Gibney, George Kypriotakis, Francesco Versace

Faculty, Staff and Student Publications

Cue-induced reward-seeking behaviors are regulated by both the affective and cognitive control systems of the brain. This study aimed at investigating how individual differences in affective and cognitive responses to cues predicting food rewards contribute to the regulation of cue-induced eating. We recorded electroencephalogram (EEG) from 59 adults while they viewed emotional and food-related images that preceded the delivery of food rewards (candies) or non-food objects (beads). We measured the amplitude of the late positive potential (LPP) in response to a variety of motivationally relevant images and power in the theta (4-8 Hz) frequency band after candies or beads were …

Lymphocytic Choriomeningitis Virus In Person Living With Hiv, Connecticut, Usa, 2021, Jonathan Dyal, Shiv Gandhi, Caitlin M Cossaboom, Austin Leach, Ketan Patel, Marjorie Golden, Joseph Canterino, Marie-Louise Landry, Debi Cannon, Mary Choi, Inna Krapiunaya, John D Klena, Trevor Shoemaker

Faculty, Staff and Student Publications

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

Long-Term Risks Of Depression And Suicide Among Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Anna Bill-Axelson, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear.

OBJECTIVE: To determine the long-term risks of major depression and death by suicide in a large population-based cohort.

DESIGN, SETTING, AND PARTICIPANTS: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard …

Clonal Evolution And Hierarchy In Myeloid Malignancies, Koichi Takahashi, Tomoyuki Tanaka

Faculty, Staff and Student Publications

Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the …

Characteristics And Clinical Outcomes Of Patients With Acute Myeloid Leukemia With Inv(3)(Q21q262) Or T(3; 3)(Q21; Q262), Guillaume Richard-Carpentier, Caitlin R Rausch, Koji Sasaki, Danielle Hammond, Kiyomi Morita, Koichi Takahashi, Guilin Tang, Rashmi Kanagal-Shamanna, Kapil Bhalla, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Elizabeth J Shpall, Amin Alousi, Naval G Daver, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis. Determinants of clinical outcomes and optimal treatment remain uncertain. We retrospectively reviewed 108 cases of AML with inv(3)/t(3;3) and evaluated clinicopathological characteristics and clinical outcomes: 53 newly diagnosed (ND) AML and 55 relapsed/refractory (R/R) AML. Median age was 55 years. White blood cell (WBC) count ≥20x109/L and platelet count ≥140x109/L was observed in 25% and 32% of ND patients, respectively. Anomalies involving chromosome 7 were identified in 56% of patients. The most frequently mutated genes were SF3B1, PTPN11, NRAS, KRAS and ASXL1. In ND patients, the composite complete remission …

T Cell Fate Decisions During Memory Cell Generation With Aging, Ines Sturmlechner, Abhinav Jain, Yunmei Mu, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

The defense against infectious diseases, either through natural immunity or after vaccinations, relies on the generation and maintenance of protective T cell memory. Naïve T cells are at the center of memory T cell generation during primary responses. Upon activation, they undergo a complex, highly regulated differentiation process towards different functional states. Naïve T cells maintained into older age have undergone epigenetic adaptations that influence their fate decisions during differentiation. We review age-sensitive, molecular pathways and gene regulatory networks that bias naïve T cell differentiation towards effector cell generation at the expense of memory and Tfh cells. As a result, …