Hematology Commons^™

Antithrombotic Strategies And Outcomes In Neonates And Infants With Cardiac Shunts: A Systematic Review And Meta-Analysis., Amy L. Kiskaddon, Neil A. Goldenberg, Marisol Betensky, Joshua W. Branstetter, Dina Ashour, Pamela Williams, Arabela C. Stock, Michael Silvey, Therese M. Giglia, Nhue L. Do, Cardiac Disease Thrombosis And Hemostasis Working Party Of The Isth Ssc Subcommittee On Pediatric And Neonatal Thrombosis And Hemostasis

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cardiac shunt thrombosis in neonates and infants remains a concern for shunt failure and mortality. The optimal strategy for thromboprophylaxis remains unknown.

OBJECTIVES: This systematic review aims to characterize antithrombotic strategies and outcomes in neonates and infants with a cardiac shunt.

METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched from inception through July 2024 for studies reporting shunt thrombosis prevalence among infants who received a cardiac shunt. We estimated the pooled prevalence of shunt thrombosis using random-effects meta-analysis. In the subgroup analysis, we evaluated the effects of shunt type and antithrombotic strategies on shunt thrombosis prevalence.

RESULTS: A total …

Outcomes And Microbiological Patterns Of Bacteremia In Chemotherapy-Related Febrile Neutropenia At A Tertiary Facility In Kenya, Abhijit Ghose, Jasmit Shah, Anne Mwirigi, Charles Makasa, Felix Riunga

Internal Medicine, East Africa

Introduction: Febrile neutropenia (FN) is a major cause of mortality and morbidity in patients with malignancy post-chmotherapy. Current guidelines for managing FN recommend starting empiric antibiotic therapy (EAT) promptly. The choice of antibiotic is based on the patient’s condition, local data on common microorganisms isolated, and their resistance patterns. Of note, there is a growing trend of isolating multi-drug–resistant gram-negative bacteria in these patients. In sub-Saharan Africa, there are insufficient data on the mortality rates of FN. There is also a lack of local epidemiologic data on the frequently isolated microorganisms and their antibiotic resistance patterns. This makes it challenging …

Mitophagy’S Impacts On Cancer And Neurodegenerative Diseases: Implications For Future Therapies, Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng

Faculty, Staff and Student Publications

Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations-such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death-remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies …

Fractional Flow Reserve From Coronary Ct: Evidence, Applications, And Future Directions, Arta Kasaeian, Mohadese Ahmadzade, Taylor Hoffman, Mohammad Ghasemi-Rad, Anoop Padoor Ayyappan

Faculty, Staff and Students Publications

Coronary computed tomography angiography (CCTA) has emerged as the leading noninvasive imaging modality for the assessment of coronary artery disease (CAD), offering high-resolution visualization of the coronary anatomy and plaque characterization. The development of fractional flow reserve derived from CCTA (FFR-CT) has further transformed the diagnostic landscape by enabling the simultaneous evaluation of both anatomical stenosis and lesion-specific ischemia. FFR-CT has demonstrated diagnostic accuracy comparable to invasive FFR. The combined use of CCTA and FFR-CT is now pivotal in a broad range of clinical scenarios, including the evaluation of stable and acute chest pain, assessment of high-risk and complex plaque …

From Imaging To Computational Domains For Physics-Driven Molecular Biology Simulations: Hindered Diffusion In Platelet Masses, Catherine House, Ziyi Huang, Kaushik Shankar, Sandra Young, Meghan Roberts, Scott Diamond, Maurizio Tomaiuolo, Timothy Stalker, Lu Lu, Talid Sinno

Cardeza Foundation for Hematologic Research

When formed in vivo, murine hemostatic thrombi exhibit a heterogeneous architecture comprised of distinct regions of densely and sparsely packed platelets. In this study, we utilize high-resolution electron microscopy alongside machine learning and physics-based simulations to investigate how such clot microstructure impacts molecular diffusivity. We used Serial Block Face - Scanning Electron Microscopy (SBF-SEM) to image select volumes of hemostatic masses formed in a mouse jugular vein, producing high-resolution 2D images. Images were segmented using machine learning software (Cellpose), whose training was augmented by manually segmented images. The segmented images were then utilized as 2D computational domains for Lattice Kinetic …

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Clinico-Epidemiological Characteristics Of Cerebral Venous Sinus Thrombosis In Kenya: A Retrospective Case Series, Taby Siika, Jaskirat Sokhi, Juzar Hooker, Sheila Waa, Anne Mwirigi, Jasmit Shah, Dilraj Sokhi

Internal Medicine, East Africa

Background: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that is more common in young, especially female, adults and can be challenging to diagnose due to its frequently non-specific presentation and diverse risk factors. Most cases are idiopathic, and international guidelines do not recommend routine investigations for underlying thrombophilia. Timely diagnosis, with prompt neuroimaging and guideline-based treatment, leads to good outcomes. However, in the literature on CVST from sub-Saharan Africa, the gap is substantial, with the few cases described as being related to systemic and/or brain infections. We describe here the largest cohort of CVST from the …

Comparison Between Acute Leukemia Screening Tube And Lineage-Specific Panels For The Diagnosis Of Acute Leukemia In Kenya, Nancy Okinda, Geoffrey Omuse, Elizabeth Kagotho, Douglas Munga

Pathology, East Africa

Purpose: Acute leukemia is a group of hematologic malignancies categorized according to the immature cells that proliferate and replace the normal bone marrow. Flow cytometry has emerged as a cornerstone in the diagnosis of hematologic malignancies. Staged analysis with a screening tube containing specific lineage markers determines the need for subsequent testing if there is an abnormal population (blasts). The specific lineage panels to be analyzed are determined depending on the positive markers in the screening tube. This study aimed to determine the agreement of diagnosis using the acute leukemia screening tube (ALST) and the lineage-specific panel.

Methods: This was …

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

Complications And Management Of Idiopathic Multicentric Castleman Disease, Kavanya Feustel, Jacob W. Keeling, Olivia Makos, Dmitriy Scherbak

HCA Healthcare Journal of Medicine

Background

The pathophysiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood compared to the other subtypes of MCD, which has contributed to limited treatment options and poor prognosis for iMCD patients. The pathogenesis of iMCD is thought to be mediated in part by dysregulation of interleukin (IL)-6.

Case Presentation

We present a case report of a 39-year-old Caucasian man with siltuximab-refractory iMCD. He presented with severe lower extremity lymphedema and wounds. His disease progressed through standard-of-care siltuximab. Due to his severe disease-related morbidity, he contracted recurrent infections, often complicated by sepsis. Ultimately, he required a left lower extremity amputation. …

Immune Thrombocytopenic Purpura Association With Epstein-Barr Virus, Amer Aldamouk, Bachr Masri, Ali Khan, Pulkita Uppal

Graduate Medical Education Research Journal

Immune thrombocytopenia (ITP), also referred to as idiopathic thrombocytopenic purpura, is an acquired form of thrombocytopenia caused by antibodies directed against platelet glycoproteins, particularly anti-GpIIb/IIIa antibodies. Epstein-Barr virus (EBV), a herpes virus infecting a large majority of the population before adulthood, has been implicated in various immune-mediated disorders, including ITP. In this report, we present a case of a young adult female with a history of thrombocytopenia who was found to have severe thrombocytopenia attributed to chronic EBV infection. Despite initial treatment with corticosteroids and intravenous immunoglobulin (IVIG), the patient's condition necessitated second-line therapies, including rituximab and thrombopoietin receptor agonists. …

Cars And Trucks: Driving A Paradigm Shift In Hematologic Malignancies, Christine Charek, Tia Solh

Lynchburg Journal of Medical Science

Hematologic malignancies account for a significant number of annual cancer diagnoses and deaths across the globe. Historically, the prognosis for relapsed and/or refractory disease after standard therapies, such as chemotherapy and/or radiation, was poor. Chimeric antigen receptor (CAR) T-cell therapy offers an additional treatment option. While promising, this type of immunotherapy also comes with potentially severe side effects, toxicities, and limitations. A better understanding of the development, administration, and management of patients undergoing treatment can provide the general clinician with the knowledge to assist within a multidisciplinary team to ultimately improve patient outcomes.

Macular Thinning And Microvasculature Abnormalities In Children With Sickle Cell Disease: A Longitudinal Analysis, Sally S. Ong, Ann Nampomba, Sara Rahman, Loka Thangamathesvaran, Grace Reilly, Jianqiao Ma, Jay Vaidya, Sophie Lanzkron, Adrienne W. Scott

Cardeza Foundation for Hematologic Research

PURPOSE: To assess longitudinal changes in retinal thickness and vessel density (VD) in pediatric sickle cell disease (SCD).

DESIGN: A prospective cohort study.

PARTICIPANTS: Children (< 18 years old) with HbSS and HbS variant (HbSC and HbS thalassemia) genotypes were enrolled from a university-based retina subspecialty clinic from 2017 to 2019 and followed for ≥2 years.

METHODS: Participants received 3 × 3 and 6 × 6 mm OCT and OCT angiography scans at baseline and at each follow-up visit.

MAIN OUTCOME MEASURES: Retinal thickness, superficial capillary plexus (SCP), and deep capillary plexus (DCP) VD were compared over time.

RESULTS: Children with HbSS (n = 14) and HbS variant (n = 14) genotypes with ≥1 follow-up were included in the study (total 56 eyes). For HbSS, rates of retinal thinning per …

A Challenging Case Of Pyruvate Kinase Deficiency Complicated By Hemophagocytic Lymphohistiocytosis, Christopher Pope, Farah Ashraf, Jacqueline White, Akhilesh Sivakumar, Eric Behling, Tulin Budak-Alpdogan

Cooper Rowan Medical Journal

Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder and the most common cause of chronic hemolytic anemia secondary to red blood cell (RBC) enzyme defects. Treatment is mainly supportive including splenectomy and transfusions. Mitapivat, an oral allosteric activator of defective pyruvate kinase, was approved by the FDA in February 2022 for treatment of adults with PKD. However, because Mitapivat undergoes liver metabolism, patients must have stable liver profiles prior to initiation of therapy. We present a case of PKD complicated by hemophagocytic lymphohistiocytosis (HLH). We initiated steroid therapy for his HLH with the intent to subsequently start Mitapivat. We …

Emerging Technologies Of Single-Cell Multi-Omics, Yi June Kim, Koichi Takahashi

Faculty, Staff and Student Publications

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in …

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

Standardizing Ngs Testing For All Pediatric Oncology Patients: A Quality Improvement Approach, Casey Treuting Md, Zachary Leblanc Md

Quality Improvement & Patient Safety Forum

No abstract provided.

Increasing The Detection Of Pediatric Oncology Patients At Risk For Malnutrition Using A Specialized Screening Tool, Casey Treuting Md, Cori A. Morrison Md, Jourdan A. Mills Rd

Quality Improvement & Patient Safety Forum

No abstract provided.

American Society Of Hematology/International Society On Thrombosis And Haemostasis 2024 Updated Guidelines For Treatment Of Venous Thromboembolism In Pediatric Patients, Paul Monagle, Muayad Azzam, Rachel Bercovitz, Marisol Betensky, Rukhmi Bhat, Tina Biss, Brian Branchford, Leonardo R. Brandão, Anthony K.C. Chan, Vincent E.S. Faustino, Julie Jaffray, Sophie Jones, Hassan Kawtharany, Bryce A. Kerlin, Nicole Kucine, Riten Kumar, Christoph Male, Marie Claude Pelland-Marcotte, Leslie Raffini, Chittalsinh Raulji, Sarah E. Sartain, Clifford M. Takemoto, Cristina Tarango, C. Heleen Van Ommen, Maria C. Velez, Sara K. Vesely, John Wiernikowski, Suzan Williams, Hope P. Wilson, Et Al

School of Medicine Faculty Publications

Background: The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials. Objective: The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH). These ASH/ISTH evidence-based guidelines are intended to support patients, clinicians, and other health care professionals in the management of pediatric patients with VTE. Methods: ASH/ISTH formed a multidisciplinary guideline panel to minimize potential bias from …

Multimodal Spatial Proteomic Profiling In Acute Myeloid Leukemia, Christopher P Ly, Ivo Veletic, Christopher D Pacheco, Enes Dasdemir, Fatima Z Jelloul, Sammy Ferri-Borgogno, Akshay V Basi, Javier A Gomez, Jessica L Root, Patrick K Reville, Sonali Jindal, Sreyashi Basu, Padmanee Sharma, Andres E Quesada, Carlos Bueso-Ramos, Taghi Manshouri, Branko Cuglievan, Miriam Garcia, Jared K Burks, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) resides in an immune-rich microenvironment, yet, immune-based therapies have faltered in eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized a high-throughput tissue-microarray-based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on a single slide, capturing immune, tumor, and structural components. Using unbiased clustering on the spatial K function, we unveiled the presence of tertiary lymphoid-like aggregates in bone marrow, which we validated using spatial transcriptomics and an independent proteomics approach. We then found validated TLS signatures predictive of outcomes in AML using an …

Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry

Research Days

Background: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome caused by ribosomal protein gene mutations leading to apoptosis of erythroid progenitors. We identified a novel heterozygous variant (c.167+769C>T) in the noncoding region of RPL30 in a patient diagnosed with DBA.

Objectives/Goal: We hypothesized that this variant stunts erythroid differentiation at the proerythroblast stage and is pathogenic for DBA.

Methods/Design: We developed an induced pluripotent stem cell (iPSC) model with a wild type (WT) and three CRISPR-Cas9 edited RPL30 mutant clones. iPSCs were differentiated into hematopoietic stem cells, which were assessed by flow cytometry and single cell …

Inpatient Thrombophilia Workup After Acute Vte: The Tests That Don’T Pay It Forward, Eliakim Munda, Bs, Ruben Rhoades, Md, Ms

Health Equity and Quality Improvement (HEQI) Summit

Background

• Venous thromboembolism is a complex multifactorial disease that is influenced by genetic, environmental and behavioral risk factors.
• Testing for inherited thrombophilia is commonly performed after a VTE event to help identify underlying genetic risk factors and assess the risk of recurrence.
• Despite clinical guidelines advising against thrombophilia testing in patients with acute VTE, these tests continue to be ordered even though lab results are unlikely to alter treatment decisions

Problem Statement

• At TJUH, activity and genetic assays are frequently ordered for patients with acute VTE during admission, increasing the likelihood of false- positive results that may lead to unnecessary …

Reducing Premedication Use With Intravenous Iron In The Outpatient Setting, Tara Rakiewicz, Liam Heneghan, Mark Attilio, Ruben Rhoades, Michael Zimmerman, Matthew Tucker, Brianna Costello, Adam Binder, Tanya Thomas

Health Equity and Quality Improvement (HEQI) Summit

Background

• Intravenous (IV) formulations of iron are safe, quick, easy to administer, and are indicated in patients with Iron Deficiency.
• Prior formulations of IV iron were associated with anaphylaxis and have since been removed from the market -- healthcare workers remain anxious about their potential for reactions
• Rate of anaphylactic reactions are about 1 in 200,000 infusions
• Current IV formulations available can be associated with a complement mediated, pseudo-allergy, that presents with flushing, myalgia/arthralgia, and chest pressure. Reactions are dependent on infusion rate and improve after stopping the infusion.
• Premedication with acetaminophen and diphenhydramine are often ordered for IV iron …

Time To Transfer - The Clock Is Ticking: A Quality Improvement Project, Tara Rakiewicz, Liam Heneghan, Brianna Costello, Matthew Tucker, Michael Zimmerman, Tanya Thomas, Jessica Sheridan, Adam Binder

Health Equity and Quality Improvement (HEQI) Summit

Background

• Thomas Jefferson University Hospital Center City (TJUH CC) campus is the predominant referral center for patients with hematologic malignancy in parts of PA, DE, and NJ
• Patients accepted for transfer to TJUH under Medical Oncology, often have longer than anticipated time to transfer (time from transfer acceptance to patient physical arrival)
• Long transfer times delay potentially lifesaving diagnostics and treatment; this can be most concerning for patients with aggressive hematologic malignancies given need for subspecialist management
• Data review from 2023-2024 showed patients with aggressive hematologic malignancy (defined as acute leukemia, chronic myeloid leukemia in blast crisis, diffuse large B …

Improving Recognition And Reporting Of Blood Transfusion Reactions In The Inpatient Setting, Tara Rakiewicz, Douglas Russ, Juliana Guarente, Katy Loos, Mary Harach, Jeffrey Riggio, Elizabeth Teixeira, Adam Binder

Health Equity and Quality Improvement (HEQI) Summit

Background

• Blood product transfusion reactions are associated with a spectrum of signs/ symptoms and can be challenging to identify. Transfusion reactions occur in about 1.1% of transfusions and constitute a significant source of iatrogenic morbidity and mortality.
• There is a nationwide under-reporting of transfusion reactions to blood transfusion Services.
• At TJUH, formally reported reactions comprised 0.24% of all blood product transfusions in 2024, similar to the national reporting average of 0.22%.
• Transfusion associated circulatory overload (TACO), and Transfusion related acute lung injury (TRALI) are two leading causes of mortality of blood transfusion reactions (Figure 1).
• Under-reporting leads to false data …

Are Hospital-Acquired Sepsis Cases Over-Reported Due To How Sepsis Is Coded In Electronic Health Records?, Michael Sakarya, Cooper Roslund, Spencer Foreman, David Gaieski, Md, Shruti Chandra, Md, Wayne Bond Lau

Health Equity and Quality Improvement (HEQI) Summit

Introduction

• Hospital-acquired sepsis (HAS) is a preventable cause of morbidity and mortality for hospitalized patients and is associated with greater cost and resource utilization compared to non-HAS.
• International Statistical Classification of Disease (ICD) coding system is used to identify HAS.
• Patients assigned HAS by ICD coding are presumed to have a nosocomial infection.
• Errors by ICD coding may cause misclassification of HAS cases.
• Unclear whether misclassified HAS have different outcomes than actual HAS

Resumption Of Anti-Platelet/Anticoagulation Therapy Following Lumbar Spine Surgery, Stephanie Serva, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Problem: There is data on AC/AP use in perioperative period for patients undergoing spine surgery and no formal established guidelines on when to resume AC/AP medications after surgery
• Aim: To determine standardized protocol for resuming antiplatelet/anticoagulation therapy following lumbar surgery and to reduce combined post-operative cardiac/cerebrovascular/thrombotic events, and post- operative hematomas by 10% in 5 years
• Population: Patients undergoing elective lumbar spine surgery who take AC/AP at home

Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski

Faculty, Staff and Student Publications

Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …

A Century Of Hypomethylating Agent: A Remarkable Response To Azacitidine Monotherapy For Relapsed Acute Myeloid Leukemia - A Case Report, Chetan Jeurkar, Amry Majeed, Lindsay Wilde, Gina Keiffer, Margaret Kasner

Department of Medical Oncology Faculty Papers

INTRODUCTION: Acute myeloid leukemia (AML) is a disease of the elderly with a median age at diagnosis of 68 and with a very poor prognosis outside of those patients who have cytogenetic and/or molecular findings which confer a better prognosis. Most fit patients are treated with chemotherapy and then allogeneic hematopoietic stem cell transplant if they are intermediate or poor risk by ELN 2022 criteria (aSCT). aSCT is the mainstay of curative treatment although many patients are not candidates due to age, performance status, and comorbidities. In patients who are not candidates for curative treatment, low-intensity chemotherapy regimens, including monotherapy …

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …