Hematology Commons^™

Reducing Clinical Trial Eligibility Barriers For Patients With Mds: An Icmds Position Statement, Uma Borate, Kelly Pugh, Allyson Waller, Rina Li Welkie, Ying Huang, Jan Philipp Bewersdorf, Maximilian Stahl, Amy E Dezern, Uwe Platzbecker, Mikkael A Sekeres, Andrew H Wei, Rena J Buckstein, Gail J Roboz, Michael R Savona, Sanam Loghavi, Robert P Hasserjian, Pierre Fenaux, David A Sallman, Christopher S Hourigan, Matteo Giovanni Della Porta, Stephen Nimer, Richard F Little, Valeria Santini, Fabio Efficace, Justin Taylor, Guillermo Garcia-Manero, Olatoyosi Odenike, Tae Kon Kim, Stephanie Halene, Rami S Komrokji, Elizabeth A Griffiths, Peter L Greenberg, Mina L Xu, Zhuoer Xie, Rafael Bejar, Guillermo F Sanz, Mrinal M Patnaik, Maria Figueroa, Hetty E Carraway, Omar Abdel-Wahab, Daniel Starczynowski, Eric Padron, Jacqueline Boultwood, Steven Gore, Naval G Daver, Jane E Churpek, Ravindra Majeti, John M Bennett, Alan F List, Andrew M Brunner, Amer M Zeidan

Faculty, Staff and Student Publications

Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly …

Unlocking Prognostic Potential: Biomarker Predictors Of Admission And Length Of Stay In Pediatric Sickle Cell Vaso-Occlusive Pain Crisis, Jeffrey Hernandez, Abhishek Dutta, Jacob Lowry, Bruce Bernstein, Luis Gamboa, Nataly Apollonsky

Tower Health Research Day

No abstract provided.

Evolution Of Btk Inhibitors, Dena Mathew

Lynchburg Journal of Medical Science

The purpose of this clinical review evaluates the evolution of bruton’s tyrosine kinase (BTK) inhibitors in becoming the standard of care in treating chronic lymphocytic leukemia (CLL). The first-generation BTK inhibitor ibrutinib has demonstrated superior efficacy over traditional chemotherapy in several randomized clinical trials in terms of progression free survival (PFS). However, due to cardiovascular toxicities of atrial fibrillation (afib), hypertension (HTN), and bleeding, have led to drug discontinuation. Second-generation BTK inhibitors, acalabrutinib and zanubrutinib have demonstrated reduced rates in cardiovascular toxicities due to improved BTK receptor selectivity, as seen in three head-to-head ibrutinib clinical trials. The emergence of BTK …

Superior Preclinical Efficacy Of Co-Treatment With Brg1/Brm And Flt3 Inhibitor Against Aml Cells With Flt3 Mutations, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K Reville, Lauren B Flores, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Kapil N Bhalla

Faculty, Staff and Student Publications

Although treatment with standard frontline therapies, including a FLT3 inhibitor (FLT3i) reduces AML burden and achieves clinical remissions, most patients with AML with FLT3 mutation relapse due to therapy-resistant stem/progenitor cells. The core ATPases, BRG1 (SMARCA4) and BRM (SMARCA2) of the canonical (c) BAF (BRG1/BRM-associated factor) complex is a dependency in AML cells, including those harboring FLT3 mutations. We have previously reported that treatment with FHD-286, a BRG1/BRM ATPases inhibitor, induces differentiation and loss of viability of AML stem/progenitor cells. Findings of present studies demonstrate that treatment with FHD-286 induces lethality in AML cells, regardless of sensitivity or resistance to …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Sa A Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Superior Vena Cava Syndrome Due To Germ Cell Tumor In A Young Adult: Case Report, Manlio F. Lara Duck, Netzahualcoyotl Mayek Pérez, Juan Rosales Martínez

Research Symposium

Background: In superior vena cava syndrome (SVCS), the superior vena cava becomes mechanically obstructed by venous thrombus formation or by compression caused by intrathoracic tumors. SVCS is most common in men over 45 years of age; 22.5% of patients with SVCS have stage IV lung cancer or lymphoma. SVCS may occur secondary to extrathoracic tumors (testicular, ovarian, kidney, intestinal).

Case presentation: Male (24 years old) with a history of cancer in his maternal grandmother; denied drug addiction. Factory worker who denied being in direct contact with any chemicals and/or toxins. He reported non-productive cough; paroxysmal unilateral left facial edema without …

Clinical Relapse Versus Treatment Failure: The Case For Surveillance For Re-Appearance Of Minimal Measurable Disease In Pediatric Patients With Higher Risk B-All, Paul S. Gaynon, Linwei Li

Research Symposium

Background: Despite significant advancements in the treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL), chemotherapy has reached its end of “intensification” stage despite improvements in supportive care. Moreover, relapse remains a major challenge, particularly in high-risk populations such as adolescents and young adults (AYAs). The definition of threshold for clinical relapse as 25% presence of marrow lymphoblasts was established decades ago, which may be incoherent with current therapeutic strategies and delay the window for timely treatment for relapsed patients. Emerging data suggest that early detection of minimal residual disease (MRD) may offer an opportunity to intervene before clinical relapse, improving …

Roles Of Mir-223 In Platelet Function And High On-Treatment Platelet Reactivity: A Brief Report And Review, Shayan Askari, Lawrence E. Goldfinger

Cardeza Foundation for Hematologic Research

BACKGROUND: Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.

OBJECTIVES: In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.

METHODS: We have …

Atypical Dengue Fever With Severe Hematological Manifestations: A Case From The Rio Grande Valley, Elias Arellano Villanueva, Alhasan Asaad, Jose Campo Maldonado

Research Symposium

Background: Dengue fever, a mosquito-borne viral illness, is endemic in tropical regions, including border regions like the Rio Grande Valley while often self-limited, severe presentations such as dengue hemorrhagic fever and dengue shock syndrome highlight its challenges and complexities. This report describes an atypical dengue case with severe hematological manifestations, underscoring the diagnostic challenges and the importance of early recognition, multidisciplinary evaluation, and evidence-based management.

Case Presentation: A 22-year-old Hispanic female with no significant past medical history presented to the ED with hematemesis and fever following her travel to Monterrey, Mexico. Initial symptoms included high fever (107.6°F), chills, diarrhea, vomiting, …

A Peculiar Pancreatitis: Investigating The Adverse Effects Of Mesalamine, Elias Arellano Villanueva, Miguel Lopez, Alhasan Asaad, Jose Campo Maldonado

Research Symposium

Background: Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospitalizations in the United States, accounting for approximately 300,000 emergency department visits annually. It is characterized by parenchymal and peripancreatic fat necrosis accompanied by inflammation. The clinical diagnosis of AP is based on elevated serum amylase and lipase levels, characteristic imaging findings, and epigastric pain often radiating to the back. While gallstones and alcohol use are the most common causes of AP, drug-induced pancreatitis (DIP) is a rare but increasingly recognized etiology, contributing to 0.1–5% of cases. DIP is typically diagnosed by excluding other causes and is often associated with …

Overlap Of Pnh With Myelodysplastic Syndrome: Diagnostic Challenges And Management Approaches, Alyssa L. Sepulveda, Ronald A. Shaju, Yolanda V. Gutierrez

Research Symposium

Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) and Myelodysplastic Syndrome (MDS) are both hematologic disorders that overlap, posing challenges in diagnosis and management. PNH involves complement-mediated hemolysis and clonal hematopoiesis, while MDS is characterized by ineffective hematopoiesis and cytopenias. Their shared features, such as clonal mutations and bone marrow failure, can complicate differentiation. Flow cytometry is essential for identifying PNH clones and guiding treatment. Understanding this overlap is key to improving outcomes through targeted therapies and advanced management strategies.

Methods: A systematic review of PubMed, Science Direct, and Cochrane was conducted for articles published between 2000 and 2025. Keywords included 'paroxysmal nocturnal …

Neurocognitive Gains Among Ugandan Children With Sickle Cell Anemia On Hydroxyurea: 18-Month Trial Interim Results, Shubaya Kasule Naggayi, Dennis Kalibbala, Vincent Mboizi, John M. Ssenkusu, Zhezhen Jin, Caterina Rosano, Deogratias Munube, Bill Wambaka, Ruth Namazzi, Robert Opoka

Paediatrics and Child Health, East Africa

Children with sickle cell anemia (SCA) frequently develop progressive neurocognitive impairment. We aimed to determine effects of hydroxyurea therapy on neurocognitive function in Ugandan children with SCA by comparing levels at enrollment to a planned 18-month interim assessment. Ugandan children (N=264) ages 3-9 years were enrolled from a SCA clinic and treated in a 30-month singlearm open-label trial with escalation to maximum tolerated dose (MTD). Primary outcome was the effects of hydroxyurea on cognition, attention and executive function, along with transcranial doppler ultrasound (TCD) blood flow velocity. Sibling controls (N=110) without SCA underwent neurocognitive testing in parallel to establish age-normalized …

Effect Of Social Determinants Of Health On Clinic Visit Attendance In Patients With Hemophilia, Shailly Gaur, Brian Lee Phd, Mph, James Anderst Md, Msci, Katie Foote Lscsw, Lcsw, Osw-C, Andrea Bradley-Ewing Mpa, Ma, Shannon L. Carpenter

Posters

Background Social determinants of health (SDOH) create barriers to seeking care regularly, especially for patients with chronic disease. Patients with moderate-severe hemophilia A and B (factor 8 and 9 deficiencies respectively) have a life-long higher risk of bleeding and require chronic therapies. Specialized care is offered through hemophilia treatment centers (HTCs); however, these can be difficult to access for some individuals. Previous SDOH research in this patient population has been limited; therefore, it can be difficult to identify the barriers to care that exist. There is a need to examine SDOH more thoroughly to create patient-directed interventions to improve access …

The Feasibility Of Pharmacokinetic-Based Dosing Of Hydroxyurea For Children With Sickle Cell Anaemia In Uganda : Baseline Results Of The Alternative Dosing And Prevention Of Transfusions Trial, Alexandra Power Hays, Ruth Namazzi, Min Dong, Caroline Kazinga, Charles Kato, Sadat Aliwuya, Kathryn Mcelhinney, Andrea L. Conroy, Adam Lane, Robert Opoka

Paediatrics and Child Health, East Africa

Pharmacokinetic (PK)-guided dosing of hydroxyurea for children with sickle cell anaemia (SCA) could optimize dosing and improve outcomes, but its feasibility has not been demonstrated in low-resource settings where the majority of affected children live. Alternative Dosing And Prevention of Transfusions (ADAPT) is a prospective trial evaluating blood transfusions and the feasibility of determining PK-guided, hydroxyurea maximum tolerated doses (MTD) for children with SCA in Uganda, using portable high-performance liquid chromatography (HPLC) and a novel PK software programme (HdxSim). ADAPT enrolled 106 participants, and 100% completed PK testing. PK-guided doses were generated for 78%, of which 38% were within the …

Case Series On Prosthetic Valve Thromboses Treated With Intravenous Thrombolysis At A Tertiary Teaching Hospital In Nairobi – Kenya, John Odhiambo, Salim Abdallah, Mzee Ngunga

Internal Medicine, East Africa

Valvular heart disease is a significant global health issue, particularly in developing countries where Rheumatic Heart Disease (RHD) is the leading cause. Valve replacement surgeries have increased, with mechanical prostheses favored for their durability. However, thromboembolism remains a critical complication post-surgery, with prosthetic valve thrombosis rates of 0.03% for bioprosthetic valves and between 0.5% to 8% for mechanical valves in the aortic and mitral position. This report details two cases of heart failure following valve replacement due to rheumatic heart disease. The first case involves a 42-year-old female who developed prosthetic valve thrombosis after discontinuing warfarin for menorrhagia postmechanical mitral …

A Phase 1 Study Of Durvalumab As Monotherapy Or Combined With Tremelimumab With Or Without Azacitidine In Patients With Myelodysplastic Syndrome, Guillermo Garcia-Manero, Manila Gaddh, Uwe Platzbecker, R Coleman Lindsley, Sarah M Larson, Timothy Chevassut, Pierre Fenaux, Rami Komrokji, Roger Lyons, Aref Al-Kali, Yu Jiang, John Bothos, Danielle M Townsley, Amer M Zeidan

Faculty, Staff and Student Publications

Upregulation of programmed death ligand-1 (PD-L1) has been observed in patients with MDS, and its expression on myeloblasts is associated with progression to AML. This open-label, phase 1 study evaluated the safety and tolerability of the PD-L1 antibody durvalumab as monotherapy (part 1) and in combination with tremelimumab, with or without azacitidine (part 2), in patients with MDS who progressed following hypomethylating agent treatment. Sixty-seven adults with MDS were enrolled (part 1, 40 with low/intermediate-1 or intermediate-2/high IPSS risk status; part 2, 27 with intermediate-2/high IPSS risk status). Primary safety endpoints included dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). …

When Two Doses Make All The Difference: The Case Of Factor V Leiden In A Young Hispanic Male, Alberto Pena, Janetly Reinoso, Liza Salloum, Khiem D. Ngo, Sobia Memon, Johanna Mora

Research Symposium

Background: Recurrent venous thromboembolism (VTE) causes a substantial burden, particularly when the cause is unclear. Traditionally VTE risks include older age, immobilization, obesity, and malignancy. When VTE recurs in a young patient without these traditional factors, genetics must be considered. Of the inherited thrombophilias, Factor V Leiden (FVL) is the most common. Normally, activated factor V combines with factor X to produce thrombin, leading to clot formation. This process is regulated by activated protein C (APC), which inactivates factor V to stop coagulation. FVL is a single-base point mutation at one of the APC cleavage sites on Factor Va and …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

A Literary Review Of Physician Approach To Patient Care: Implications In Cancer Care, Daniel Ramirez, Kinsley Batson

Annual Research Symposium

No abstract provided.

Status Of Abortion Curriculum In Genetic Counseling: Survey Of Graduate Programs And Recent Graduates In The United States, Gina Sanchez, S Shahrukh Hashmi, Erica Bednar, Sarah Horvath, Bhavik Kumar, Katelynn Sagaser, Claire N Singletary, Aarti Ramdaney

Faculty, Staff and Student Publications

Genetic counselors (GCs) are trained to help individuals navigate the medical and psychological implications of genetic test results, familial conditions, and ultrasound anomalies. Therefore, familiarity with reproductive options, including abortion, is vital. However, previous studies have found gaps in GCs' knowledge regarding abortion care and there are currently no recommendations regarding abortion curriculum. This study aimed to assess the state of abortion curriculum in genetic counseling graduate programs in the United States and to examine and compare the satisfaction levels of program representatives and recent graduates. Program representatives and recent graduates were invited to complete an anonymous survey evaluating the …

Mayo Genetic Risk Models For Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent, Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen Mccullough, Fnu Aperna, Isla M Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney Dinardo, Tapan Kadia, Ayalew Tefferi

Faculty, Staff and Student Publications

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53

All Three Supersystems-Nervous, Vascular, And Immune-Contribute To The Cortical Infarcts After Subarachnoid Hemorrhage, Jens P Dreier, Alexander Joerk, Hiroki Uchikawa, Viktor Horst, Coline L Lemale, Helena Radbruch, Devin W Mcbride, Peter Vajkoczy, Ulf C Schneider, Ran Xu

Faculty, Staff and Student Publications

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical …

Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba

School of Medicine Faculty Publications

Background. We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials. Methods. The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and …

Transcription Factor Runx1 Regulates Coagulation Factor Xiii-A (F13a1): Decreased Platelet-Megakaryocyte F13a1 Expression And Clot Contraction In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Natthapol Songdej, Liying Guan, Guangfen Mao, Lawrence E. Goldfinger, Jeremy G.T. Wurtzel, Kiwon Lee, Michele P. Lambert, Mortimer Poncz, A. Koneti Rao

Cardeza Foundation for Hematologic Research

BACKGROUND: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocy- topenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased F13A1, encoding for the A subunit of factor (F)XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.

OBJECTIVES: o understand RUNX1 regulation of F13A1 expression in platelets/mega- karyocytes and the mechanisms and consequences of decreased F13A1 in RHD.

METHODS: We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown …

Hyperleukocytosis In A Neuroblastoma Patient After Treatment With Natural Killer T Cells Expressing A Gd2-Specific Chimeric Antigen Receptor And Il-15, Gengwen Tian, Amy N Courtney, Hangjin Yu, Saleh Bhar, Xin Xu, Gabriel A Barragán, Claudia Martinez Amador, Nisha Ghatwai, Michael S Wood, Deborah Schady, Antonino Montalbano, Shantan Reddy, Aoife M Roche, David De La Cerda, Donald Williams Parsons, Erica J Di Pierro, Frederic D Bushman, Andras Heczey, Leonid S Metelitsa

Faculty, Staff and Students Publications

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). This patient was the first to be treated on dose level (DL) 5 and the first patient whose product was restimulated with K562-derived artificial antigen-presenting cells (aAPCs) instead of autologous peripheral blood mononuclear cells …

Antihypertensive Potential Of Euphorbia Hirta And Leptadenia Hastata In Adrenaline-Induced Wistar Rats, Fagbohun Oyenike Bushirat, Emmanuel Ogar Ochonung, Messiah Innocent Atapia, Hassan Abdulsalam Adewuyi, Sakariyau Aido Waheed, Adebimpe Oluwatoyin Hameedah, Chizoba Victory Obunadike, Adeleye Adegboyega Edema, Samad Hussein, Abiola Mohammed Usman, Tolulope Olukayode Jaiyeola

Chemistry & Biochemistry Faculty Publications

Background: Hypertension is a major public health concern worldwide, contributing to cardiovascular morbidity and mortality. The use of plant-based therapies, such as Euphorbia hirta and Leptadenia hastata, has gained attention for their potential antioxidant, anti-hyperlipidemic, and organ-protective effects.

Objectives: This study aimed to investigate the phytotherapeutic approach to hypertension using E. hirta and L. hastata extracts in adrenaline-induced hypertensive Wistar rats

Methods: Utilizing an adrenaline-induced hypertensive rat model, we assessed the effects of E. hirta and L. hastata leaf extracts (50, 100, and 200 mg/kg) on systolic blood pressure, renal function, lipid metabolism, and hematological parameters.

Results: Antioxidant activity: …

Recombinant Factor Viia: New Insights Into The Mechanism Of Action Through Product Innovation, Miguel A Escobar, Maureane Hoffman, Giancarlo Castaman, Cedric Hermans, Johnny Mahlangu, Johannes Oldenburg, Charles L Percy, Mark T Reding, Amy D Shapiro, Steven W Pipe

Faculty, Staff and Student Publications

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X …

Integrative Genomic And Transcriptomic Analysis Reveals Targetable Vulnerabilities In Angioimmunoblastic T-Cell Lymphoma, Alyssa Bouska, Weiwei Zhang, Sunandini Sharma, Harald Holte, Rauf Shah, Waseem G. Lone, Mahfuza Afroz Soma, Ruimeng Yang, Xuxiang Liu, Syed Mehmood, Ravneet Singh Chawla, Luca Vincenzo Cappelli, Danilo Fiore, Qiang Gong, Tayla B. Heavican-Foral, Jeffrey J. Cannatella, Catalina Amador, Aiza Arif, Lynette M. Smith, Soon Thye Lim, Choon Kiat Ong, Andrew L. Feldman, Ming-Qing Du, Anamarija M. Perry, Laurence De Leval, Timothy C. Greiner, Kai Fu, Gunhild Trøen, Daniel Vodák, Sigve Nakken, Jan Delabie, David Weinstock, Stefano Pileri, Antonella Laginestra, Kyeongjin Kim, Utpal Pajvani, Julie M. Vose, Dennis D. Weisenburger, Steven M. Horwitz, Sandeep Dave, Joseph Khoury, Giorgio Inghirami, Wing C. Chan, Javeed Iqbal

Journal Articles: Oncology and Hematology

Nodal follicular helper T-cell (T_FH) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole-exome sequencing (n = 124), transcriptomic (n = 78), and methylation (n = 40) analysis, we identified recurrent mutations in known epigenetic drivers (TET2, DNMT3A, IDH2^R172) and novel ones (TET3, KMT2D). TET2, IDH2^R172, DNMT3A co-mutated AITLs had poor prognosis (p < 0.0001). Genes regulating T-cell receptor (TCR) signaling (CD28, PLCG1, VAV1, FYN) or activation (RHOA^G17V) or regulators of the PI3K-pathway (PIK(3)C members, PTEN, PHLPP1, PHLPP2) were mutated. CD28 mutation/fusion was associated with poor prognosis (p = 0.02). WES of purified, neoplastic T-cell (CD3⁺PD1⁺) demonstrated high concordance with …

Serglycin Controls Megakaryocyte Retention Of Platelet Factor 4 And Influences Megakaryocyte Fate In Bone Marrow, Joshua Lykins, Isabelle C. Becker, Virginia Camacho, Hammodah Rawhi Hammodah Alfar, Joonwoo Park, Joseph Italiano, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Megakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)/CXCL4. Here, we show that the intra-α-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN–/– MKs released ~80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)/protein interactions. In …