Hematology Commons^™

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Uday Popat, Jeremy Ramdial, May Daher, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Unique Challenges To Diagnosing Human Herpesvirus-6 (Hhv-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case And Brief Review, Harrison Zhu, Amir Ali, Karrune V Woan, Eric Tam, George Yaghmour, Alan Flores, Preet Chaudhary

Faculty, Staff and Students Publications

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, …

Clonal Hematopoiesis Analyses In Clinical, Epidemiologic, And Genetic Aging Studies To Unravel Underlying Mechanisms Of Age-Related Dysfunction In Humans, Kenneth Walsh, Nalini Raghavachari, Candace Kerr, Alexander G Bick, Steven R Cummings, Todd Druley, Cynthia E Dunbar, Giulio Genovese, Margaret A Goodell, Siddhartha Jaiswal, Jaroslaw Maciejewski, Pradeep Natarajan, Anastasia V Shindyapina, Alan R Shuldiner, Erik B Van Den Akker, Jan Vijg

Faculty, Staff and Students Publications

Aging is characterized by increased mortality, functional decline, and exponential increases in the incidence of diseases such as cancer, stroke, cardiovascular disease, neurological disease, respiratory disease, etc. Though the role of aging in these diseases is widely accepted and considered to be a common denominator, the underlying mechanisms are largely unknown. A significant age-related feature observed in many population cohorts is somatic mosaicism, the detectable accumulation of somatic mutations in multiple cell types and tissues, particularly those with high rates of cell turnover (e.g., skin, liver, and hematopoietic cells). Somatic mosaicism can lead to the development of cellular clones that …

An Unusual Case Of Breast Implant-Associated Anaplastic Large Cell Lymphoma, Sarah Premji, Andreia Barbieri, Christine Roth, Eric M Rohren, Gustavo Rivero, Sravanti P Teegavarapu

Faculty, Staff and Students Publications

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare disease entity associated with textured breast implants. Though the clinical course is typically indolent, BIA-ALCL can occasionally invade through the capsule into the breast parenchyma with spread to the regional lymph nodes and beyond including chest wall invasive disease.

CASE: We present the case of a 51-year-old female with a history of bilateral silicone breast implants placed approximately twenty years ago who presented with two months of progressively enlarging right breast mass. Ultrasound-guided biopsy of right breast mass and right axillary lymph node showed CD 30-positive

CONCLUSION: Treatment guidelines …

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Central Line Associated Bloodstream Infection Caused By Kodamaea Ohmeri In A Young Child, Amier Haidar, Farhana Khaja, Brian Simms, Amr Issam Elgehiny, Tracy Omoegbele, Nikita Khetan

Faculty, Staff and Student Publications

INTRODUCTION:

CASE REPORT: The patient is a 5-year-old male with a history of short gut syndrome, and total parenteral nutrition (TPN) dependence who presented to the emergency room with a two-day history of productive-cough, rhinorrhea, and fever. Antibiotic therapy was initiated with cefepime and vancomycin for suspected CLABSI. However, within the first twenty-four hours of his admission, his initial blood culture from his central venous catheter became positive for yeast so fluconazole was added due to suspicion of candidemia. During his admission, his initial central line and peripheral blood culture were later speciated as

CONCLUSIONS: This case report further acknowledges …

Occlusive Pulmonary Artery Thrombosis In A Healthy Neonate With No Identifiable Risk Factors, Cynthia Laviolette, Jason Turner, Latasha Lewis, Song-Gui Yang, Tim Pettitt, Kurt D Piggott

Faculty, Staff and Student Publications

Pulmonary artery thrombosis is reported in neonates with risk factors for hypercoagulability. No consensus exists regarding standard therapy for this condition. We present a neonate, with no risk factors for thrombosis, who was admitted after birth to the Pediatric Cardiac Intensive Care Unit with an occlusive left pulmonary artery thrombus.

Platelet And Erythrocyte Extravasation Across Inflamed Corneal Venules Depend On Cd18, Neutrophils, And Mast Cell Degranulation, Angie De La Cruz, Aubrey Hargrave, Sri Magadi, Justin A Courson, Paul T Landry, Wanyu Zhang, Fong W Lam, Monica A Bray, C Wayne Smith, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Student Publications

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs …

Prospective Patient-Reported Symptom Profiles Associated With Pediatric Acute Lymphoblastic Leukemia Relapse, Austin L Brown, Kimberly P Raghubar, Olga A Taylor, Melanie Brooke Bernhardt, Lisa S Kahalley, Wei Pan, Philip J Lupo, Marilyn J Hockenberry, Michael E Scheurer

Faculty, Staff and Students Publications

PURPOSE: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

METHODS: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% …

Structure, Function And Inhibition Of Critical Protein-Protein Interactions Involving Mixed Lineage Leukemia 1 And Its Fusion Oncoproteins, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. Dysregulation of MLL1 leads to overexpression of certain Hox genes and eventually leukemia initiation. Chromosome translocations involving MLL1 cause ~ 75% of acute leukemia in infants and 5-10% in children and adults with a poor prognosis. Targeted therapeutics against oncogenic fusion MLL1 (onco-MLL1) are therefore needed. Onco-MLL1 consists of the N-terminal DNA-interacting domains …

Targeting Nsd2-Mediated Src-3 Liquid-Liquid Phase Separation Sensitizes Bortezomib Treatment In Multiple Myeloma, Jing Liu, Ying Xie, Jing Guo, Xin Li, Jingjing Wang, Hongmei Jiang, Ziyi Peng, Jingya Wang, Sheng Wang, Qian Li, Linquan Ye, Yuping Zhong, Qiguo Zhang, Xiaozhi Liu, David M Lonard, Jin Wang, Bert W O'Malley, Zhiqiang Liu

Faculty, Staff and Students Publications

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone …

Bax 335 Hemophilia B Gene Therapy Clinical Trial Results: Potential Impact Of Cpg Sequences On Gene Expression, Barbara A Konkle, Christopher E Walsh, Miguel A Escobar, Neil C Josephson, Guy Young, Annette Von Drygalski, Scott W J Mcphee, R Jude Samulski, Ivan Bilic, Maurus De La Rosa, Birgit M Reipert, Hanspeter Rottensteiner, Friedrich Scheiflinger, John C Chapin, Bruce Ewenstein, Paul E Monahan

Faculty, Staff and Student Publications

Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 gene into liver cells. This phase 1/2, open-label dose-escalation study investigated BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), an adeno-associated virus serotype 8 (AAV8)-based FIX Padua gene therapy, in patients with hemophilia B. This report focuses on 12-month interim analyses of safety, pharmacokinetic variables, effects on FIX activity, and immune responses for dosed participants. Eight adult male participants (aged 20-69 years; range FIX activity, 0.5% to 2.0%) received 1 of 3 BAX 335 IV doses: 2.0 × 1011; …

Links Between Thrombosis And Inflammation In Traumatic Brain Injury, W Brad Hubbard, Jing-Fei Dong, Miguel A Cruz, Rolando E Rumbaut

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) continues to be a major healthcare problem and there is much to be explored regarding the secondary pathobiology to identify early predictive markers and new therapeutic targets. While documented changes in thrombosis and inflammation in major trauma have been well described, growing evidence suggests that isolated TBI also results in systemic alterations in these mechanisms. Here, we review recent experimental and clinical findings that demonstrate how blood-brain barrier dysfunction, systemic immune response, inflammation, platelet activation, and thrombosis contribute significantly to the pathogenesis of TBI. Despite advances in the links between thrombosis and inflammation, there is a …

Correlation Between Concentrations Of Four Heavy Metals In Cord Blood And Childhood Blood Of Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Manouchehr Hessabi, Jan Bressler, Shezeen Gillani, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

This study investigated whether the concentrations of four metals [lead (Pb), mercury (Hg), manganese (Mn), and aluminum (Al)] are correlated in cord blood and childhood blood samples from Jamaican children. Cord blood samples were obtained from 21 pregnant women enrolled in the second Jamaican Birth Cohort Study from July 1, 2011 to September 30, 2011, and blood samples were drawn from their children who participated in a follow up study when the children were 4–8 years old. Correlations were assessed by the Pearson or the Spearman’s rank correlation coefficient. The mean ages of children at the childhood visit and their …

Small-Molecule Inhibitor Of Af9/Enl-Dot1l/Af4/Aff4 Interactions Suppresses Malignant Gene Expression And Tumor Grow, Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song

Faculty, Staff and Students Publications

Chromosome translocations involving mixed lineage leukemia (MLL) gene cause acute leukemia with a poor prognosis. MLL is frequently fused with transcription cofactors AF4 (~35%), AF9 (25%) or its paralog ENL (10%). The AHD domain of AF9/ENL binds to AF4, its paralog AFF4, or histone-H3 lysine-79 (H3K79) methyltransferase DOT1L. Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and the catalytic activity of DOT1L are essential for MLL-rearranged leukemia. Protein-protein interactions (PPI) between AF9/ENL and DOT1L/AF4/AFF4 are therefore a potential drug target.

Methods: Compound screening followed by medicinal chemistry was used to find inhibitors of such PPIs, which were examined for their biological …

Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai-Lin Wang, Mei-Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Hassan B Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Hannah Choe, Edward Copelan, Corey Cutler, Moussab B Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, César O Freytes, Aaron T Gerds, Usama Gergis, Michael R Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T Kamble, Muhammad Waqas Khan, Mohamed A Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Hongtao Liu, David I Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Neil Palmisiano, Sagar S Patel, Mrinal M Patnaik, Attaphol Pawarode, Miguel-Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M Sandmaier, Bipin N Savani, Sachiko Seo, Nirav N Shah, Geoffrey L Uy, David Valcárcel, Leo F Verdonck, Edmund K Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A Yared, Wael Saber

Faculty, Staff and Students Publications

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival …

Burden-Of-Illness Associated With Bleeding-Related Hospitalizations In Atrial Fibrillation Patients: Findings From The Nationwide Readmission Database, Benjamin Miao, Monique Miller, Belinda Lovelace, Anne Beaubrun, Kelly Mcneil-Posey, Mark J Alberts, William Frank Peacock, Olivia S Costa, Charles Michael White, Craig I Coleman

Faculty, Staff and Students Publications

Introduction  A paucity of contemporary data examining bleeding-related hospitalization outcomes in atrial fibrillation (AF) patients exists.

Methods  Adults in the Nationwide Readmissions Database (January 2016–November 2016) with AF and hospitalized for intracranial hemorrhage (ICH), gastrointestinal, genitourinary, or other bleeding were identified. Association between bleed types and outcomes were assessed using multivariable regression (gastrointestinal defined as referent) and reported as crude incidences and adjusted odds ratios (ORs) or mean differences with 95% confidence intervals (CIs).

Results  In total, 196,878 index bleeding-related hospitalizations were identified in this AF cohort (CHA2DS2VASc score ≥2 in 95.1%), with 70.8% classified as gastrointestinal. The overall incidences …

Preclinical Studies Of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml), Vivian Salama

Dissertations and Theses (Open Access)

LY3410738, a novel covalent Isocitrate Dehydrogenase 1 (IDH1) inhibitor in Acute Myeloid Leukemia, it is more effective than Ivosidenib (AG120) and has a potent anti-leukemic effect against IDH1 mutant acute myeloid leukemia in combination with Venetoclax (ABT-199).

Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the citric acid cycle. Somatic gain-of-function mutations in IDH1 occur in ~10% of the newly diagnosed AML patients. The neo-enzymatic activity of mutant IDH1 results in accumulation …

Assessing Patient Attitudes To Ward Genetic Testing For Hereditary Hematologic Malignancy, Addison Johnson

Dissertations and Theses (Open Access)

Since 2003, more than 15 genes have been identified to predispose to hereditary hematologic malignancy (HHM). Although the diagnostic yield of germline analysis for leukemia is similar to solid tumors, referral for genetic evaluation in adults with leukemia is underperformed. Identifying HHM is important for prognostication, treatment, and donor selection for hematopoietic stem cell transplant. No studies have examined leukemia patients’ attitudes toward genetic testing for HHM. This study aimed to assess leukemia patients’ attitudes toward genetic testing and elicit current perceived distress due to a leukemia diagnosis. Data were elicited through an electronic survey sent to 5,513 patients diagnosed …

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

An In Vivo Genome-Wide Crispr Screen Identifies The Rna-Binding Protein Staufen2 As A Key Regulator Of Myeloid Leukemia, Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L Van Nostrand, Brian A Yee, Steven M Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G Oehler, H Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W Yeo, Tannishtha Reya

Faculty, Staff and Students Publications

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. In a newly developed knockout mouse, loss of Stau2 led to a profound decrease in leukemia growth and improved survival in mouse models of the disease. Further, Stau2 was required for growth of primary human blast crisis chronic myeloid leukemia and acute myeloid leukemia. Finally, …

Prevalence And Predictors Of Chronic Pain Intensity And Disability Among Adults With Sickle Cell Disease, Nadine Matthie, Coretta Jenerette, Ashley Gibson, Sudeshna Paul, Melinda Higgins, Lakshmanan Krishnamurti

Faculty, Staff and Student Publications

Among 170 adults with sickle cell disease, we evaluated chronic pain impact and disability prevalence, assessed age and gender differences, and identified psychosocial predictors of chronic pain intensity and disability. Most participants had a high level of disability. Chronic pain intensity and disability were significantly associated with pain catastrophizing and chronic pain self-efficacy, and worsened with age. Further research is needed to confirm study findings and develop interventions, including palliative care approaches that address catastrophizing and disability, particularly for young women and middle-aged adults with sickle cell disease. Moreover, consistent clinical assessment of chronic pain and psychosocial health should be …

Educational Case: Systemic Mastocytosis With An Associated Hematological Neoplasm, Brenda Mai, Md A Wahed, Lei Chen, Nghia D Nguyen, Xiaohong Iris Wang, Zhihong Hu

Faculty, Staff and Student Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Infant With Protein C Deficiency And Stroke In The Setting Of Iron Deficiency Anemia, Tahseen Jalal Karim, Dustin J Paul, Regina M Troxell, Rajan Patel, Ian J Butler

Faculty, Staff and Student Publications

We report an 18-month-old infant with ischemic stroke, neurocognitive impairment, and psychomotor retardation in the setting of severe iron deficiency anemia. Although an uncommon outcome in anemic children, stroke is important to consider as a cause for developmental delay in children with iron deficiency anemia.

In Vitro Characterization Of Sonothrombolysis And Echocontrast Agents To Treat Ischemic Stroke, Himanshu Shekhar, Robert T Kleven, Tao Peng, Arunkumar Palaniappan, Kunal B Karani, Shaoling Huang, David D Mcpherson, Christy K Holland

Faculty, Staff and Student Publications

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized …

Patient Attitudes To Ward Genetic Testing For Inherited Predispositions To Hematologic Malignancies, Taylor Beecroft

Dissertations and Theses (Open Access)

Although inherited predispositions to hematologic malignancies have previously been considered extremely rare, approximately 12 causative genes have been implicated in the last decade. Since individuals diagnosed with leukemia have not historically been considered for evaluation of inherited predispositions, genetic testing is underperformed in this population. This study used focus group discussions to explore the attitudes, motivations, and barriers to genetic testing for 23 patients with leukemia. Participants generally exhibited a positive regard for the utility of genetic testing, and were primarily motivated by concern for their family and a sense of altruism toward all leukemia patients. While drawbacks and barriers …