Genetic Phenomena Commons^™

Intentional Creation Of Suboptimal, Realistic Dose Distributions, Skylar S Gay, Mary P Gronberg, Raymond Mumme, Beth M Beadle, Anuja Jhingran, Tze Yee Lim, Zhiqian H Yu, Christine Chung, Meena Khan, Chelsea Pinnix, Sanjay Shete, Brent Parker, Tucker J Netherton, Carlos E Cardenas, Laurence E Court

Faculty, Staff and Student Publications

Background: Radiation oncology residents report a lack of understanding and confidence in assessing radiotherapy plan quality. A contributing factor is the environment in which plan review is taught during residency, that is, routine clinical practice, which does not provide ample time for self-guided practice in a low-stakes setting. Expertise in plan review requires diverse case presentation and many examples, which are often not achievable in smaller programs and for less common cancer types. As plan quality affects patient outcomes, it is important to address these pitfalls in the education of residents on plan review.

Purpose: To address the identified pitfalls …

Acute And Chronic Nasal Inflammation Induces Lymphangiogenesis In The Olfactory Mucosa In Mice, Suzuho Komaki, Ryuichi Imai, Yuzuki Sugimoto, Rei Settsu, Aki Obara, Atsuyoshi Shimada, Robert Dantzer, Geoffroy Laumet, Fumiaki Imamura, Sanae Hasegawa-Ishii

Faculty, Staff and Student Publications

Background: Lymphangiogenesis, the formation of new lymphatic vessels, is primarily driven by VEGF-C-mediated activation of VEGFR-3 and plays a critical role in immune regulation and tissue repair. Although lymphangiogenesis has been well documented in various inflamed tissues, its occurrence and spatiotemporal characteristics in the olfactory mucosa during nasal inflammation remain poorly understood. To address this, we investigated the localization and development of lymphatic vessels in a mouse model of both acute and chronic nasal inflammation.

Methods: Acute inflammation was induced by intranasal administration of lipopolysaccharide (LPS; 10 μg per nostril) in 8-week-old male mice, with saline-treated mice as controls. Behavioral …

Outcomes And Patterns Of Relapse Of Npm1 Mutated Acute Myeloid Leukemia Treated With Venetoclax Based Therapies, Wei-Ying Jen, Sanam Loghavi, Alexandre Bazinet, Alex Bataller, Ian Bouligny, Naval G Daver, Ghayas C Issa, Naszrin Arani, Emmanuel Almanza Huante, Abhishek Maiti, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas J Short, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo, Tapan M Kadia

Faculty, Staff and Student Publications

No abstract provided.

A Tour Of Leukemia Progress In 2025, Viewed Through The Md Anderson Leukemia Research Lens, Hagop M Kantarjian, Gautam Borthakur, Naval Daver, Courtney Dinardo, Guillermo Garcia-Manero, Ghayas Issa, Elias Jabbour, Nitin Jain, Tapan Kadia, Sanam Loghavi, Farhad Ravandi, Guilin Tang, Mary Alma Welch, William Wierda

Faculty, Staff and Student Publications

Advances in the prognostication, monitoring, and treatment of both the acute and chronic leukemias have led to drastically improved outcomes over the past 2 decades. With the advent of targeted therapies, including antibodies such as blinatumomab and inotuzumab and small molecule inhibitors, such as the BCR::ABL1 tyrosine kinase inhibitors, Bruton tyrosine kinase inhibitors, and venetoclax, the treatment landscape of leukemia has drastically changed, improving survival outcomes while relying less on overall chemotherapy intensity in many leukemia types. This progress has allowed the categorization of more leukemia types as favorable (i.e., chronic lymphocytic leukemia, younger acute lymphoblastic leukemia [patients younger than …

Brain-Wide Patterns Of Crf Receptor 1 Expression In The Transgenic Crfr1-Cre-2a-Tdtom Rat, Douglas S Engelke, Lierni Ugartemendia, Jonathan Tao, Shivakumar Rajamanikam, Fabricio H Do Monte, Nicholas J Justice

Faculty, Staff and Student Publications

The ability to manipulate neurons that express corticotropin-releasing factor (CRF) or its receptors has led to many new discoveries about how CRF signaling modulates stress-related behaviors in mice. However, similar advances in rats have been limited by the lack of reporter lines targeting CRF receptors, restricting access to behavioral paradigms that are more suitable for, or specific to, rats. Here, we provide an extensive neuroanatomical characterization of a recently generated CRFR1-Cre rat. We show that Cre and tdTomato are expressed in a pattern that closely aligns with previously reported CRFR1 expression patterns, as determined by in situ hybridization in rats …

Probabilistic Template Matching For Detecting Resting-State Functional Mri Language Network In Brain Tumor Patients, Jian Ming Teo, Vinodh A Kumar, Alexander M Khalaf, Kyle R Noll, Sherise D Ferguson, Chibawanye I Ene, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Intersubject variation among patients with brain tumors complicates the template matching process for detecting the resting-state (rs) functional MRI (fMRI) language network when using independent component analysis (ICA).

Purpose: This study aimed to develop methods that use a probabilistic language atlas to incorporate intersubject variation in brain tumor patients into the template matching process.

Methods: This retrospective study included 79 patients with brain tumors (average age, 50 ± 15 years) who underwent presurgical task-based (tb)-fMRI and rs-fMRI at clinical 3T scanners. At varying template generation thresholds (τ), binary and probabilistic templates were obtained from the language atlas. A binary …

Tagraxofusp, A Cd123-Targeted Therapy, For Chronic Myelomonocytic Leukemia: Final Results Of A Phase 1/2 Study, Mrinal M Patnaik, Haris Ali, Eunice S Wang, Abdulraheem Yacoub, James M Foran, Vikas Gupta, Gary J Schiller, Don Ambrose Stevens, Moshe Talpaz, Sarah Wall, Terra L Lasho, Abhishek A Mangaonkar, Talha Badar, Ross Lindsay, Antonio Galleu, Ira Gupta, Naveen Pemmaraju, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic neoplasm characterized by an expansion of CD123+ monocytes and plasmacytoid dendritic cells (pDCs). pDC bone marrow clusters in CMML have been associated with higher rates of acute myeloid leukemia transformation. We evaluated tagraxofusp, a CD123-targeted therapy, in a phase 1/2 trial for patients with CMML. There were no dose-limiting toxicities. At the recommended phase 2 dose of 12 μg/kg per day, 37 patients were treated: 15 were treatment naïve; 22 had relapsed/refractory disease (median number of previous therapies, 1 [range, 1-7]). Common nonhematologic treatment-emergent adverse events (AEs) included fatigue (49%), hypoalbuminemia (46%), …

Meeting Report From The 2024 Symposium On Irak4 In Cancer: Highlights And Clinical Updates, Eric S Winer, Marina Konopleva, Han W Tun, Kian-Huat Lim, Bently Doonan, Klaus H Metzeler, Lakshmi Nayak, Andrés J M Ferreri, Christina Von Roemeling, Grzegorz S Nowakowski, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a serine/threonine kinase that mediates interleukin-1 and Toll-like receptor (TLR) signaling. IRAK4 drives the activation of nuclear factor kappa B (NF-κB), which promotes cell survival, inflammation, and proliferation. Aberrant activation of IRAK4 and TLR signaling has been implicated in multiple malignancies. At the 3rd Annual IRAK4 in Cancer Symposium, experts discussed the role of IRAK4 in cancer biology, the potential for synergism between IRAK4 inhibition and other treatments to overcome resistance, and how IRAK4 inhibition may improve clinical outcomes. Preclinical data were presented demonstrating the activity of IRAK4 inhibition alone or in combination with …

Sars-Cov-2 Mrna Vaccines Sensitize Tumours To Immune Checkpoint Blockade, Adam J Grippin, Christiano Marconi, Sage Copling, Nan Li, Chen Braun, Cole Woody, Elliana Young, Priti Gupta, Min Wang, Annette Wu, Seong Dong Jeong, Dhruvkumar Soni, Frances Weidert, Chao Xie, Eden Goldenberg, Andrew Kim, Chong Zhao, Anna Devries, Paul Castillo, Rishabh Lohray, Michael K Rooney, Benjamin R Schrank, Yifan Wang, Yifan Ma, Enoch Chang, Ramez Kouzy, Kyle Dyson, Jordan Jafarnia, Nina Nariman, Gregory Gladish, Jacob New, Ada Argueta, Diana Amaya, Nagheme Thomas, Andria Doty, Joe Chen, Nikhil Copling, Gabriel Alatrash, Julie Simon, Alicia Bea Davies, William Dennis, Richard Liang, Jeff Lewis, Xiong Wei, Waree Rinsurongkawong, Ara A Vaporciyan, Andrew Johns, D3code Team, Jack Lee, Ji-Hyun Lee, Ryan Sun, Padmanee Sharma, Hai Tran, Jianjun Zhang, Don L Gibbons, Jennifer Wargo, Betty Y S Kim, John V Heymach, Hector R Mendez-Gomez, Wen Jiang, Elias J Sayour, Steven H Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity1–9. Although personalized mRNA cancer vaccines sensitize tumours to ICIs by directing immune attacks against preselected antigens, personalized vaccines are limited by complex and time-intensive manufacturing processes10–14. Here we show that mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to ICIs. In preclinical models, SARS-CoV-2 mRNA vaccines led to a substantial increase in type I interferon, enabling innate immune cells to prime CD8+ T cells that target tumour-associated antigens. Concomitant ICI treatment is required for …

Continuous Androgen Deprivation Therapy With Or Without Metastasis-Directed Therapy For Oligometastatic Prostate Cancer: The Multicenter Phase 2 Randomized Extend Trial, Alexander D Sherry, Bilal A Siddiqui, Cara Haymaker, Bryan M Fellman, Marina N Medina-Rosales, Tharakeswara K Bathala, Shuqi Wang, Suyu Liu, Aaron Seo, Kieko Hara, Hsinyi Lu, Patricia Troncoso, Stephen G Chun, Chul S Ha, Lauren L Mayo, Henry Mok, Ryan J Park, Brian F Chapin, Ryan M Phillips, Matthew P Deek, Craig A Kovitz, Ana Aparicio, Amado J Zurita, Patrick G Pilie, Lorenzo Cohen, Seungtaek L Choi, Alexandre Reuben, Phuoc T Tran, Paul G Corn, Sumit K Subudhi, Chad Tang

Faculty, Staff and Student Publications

Background and objective: Oligometastatic prostate cancer (omPC) is characterized by limited metastases. We hypothesized that metastasis-directed therapy (MDT) to all sites of omPC combined with androgen deprivation therapy (ADT) would improve clinical outcomes.

Methods: In the multicenter phase 2 EXTEND trial, patients with omPC were randomized 1:1 to ADT versus MDT + ADT in two independently powered and randomized baskets, one using intermittent ADT and one using continuous ADT. The primary endpoint was progression-free survival (PFS). The secondary endpoints included radiologic PFS (rPFS) and castration resistance-free survival (CRFS). Here, the primary results of the continuous ADT basket, the combined analysis …

Rank-Based Learning: A Novel High-Throughput Algorithm Resilient To Missing Data And Effective For Datasets With Small Sample Size, Lulu Song, Hamid Khoshfekr Rudsari, Johannes F Fahrmann, Jody Vykoukal, Sam Hanash, James P Long, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

High-throughput omics data present challenges for binary classification due to platform variability, batch effects, missing values, and high dimensionality. This study presents a novel Rank-Based Learning (RBL) method that leverages relative feature rankings to improve robustness and generalizability. We evaluated RBL against established methods like Logistic Regression (LR) and Random Forest (RF) using simulated data and two real-world plasma proteomics datasets: early-stage small cell lung cancer (SCLC) and duodenopancreatic neuroendocrine tumors (dpNET) in patients with Multiple Endocrine Neoplasia type 1 (MEN1). In simulation experiments, RBL outperformed LR under conditions involving batch effects, missing data, and varying numbers of true differential …

Protein Kinase Giα Oxidation Negatively Regulates Antibody Production By B Cells, Hyun-Ju Cho, Rebecca L Charles, Oleksandra Prysyazhna, Sapna Arjun, Asvi A Francois, Kevin M Mcbride, Philip Eaton

Faculty, Staff and Student Publications

Endogenous oxidants induce a C42-dependent interprotein disulfide between the subunits of protein kinase G (PKG) Iα in cardiovascular tissues to control blood pressure and ventricular relaxation during diastole. PKGIα is expressed in other cell types, including those of the immune system, where the redox state of this kinase is likely to regulate other important physiological processes. The role of PKGIα oxidation in antibody production by B cells, which produce oxidants such as hydrogen peroxide during differentiation, was examined by comparing the immune response of oxidation-resistant C42S PKGIα knock-in (KI) mice to their wild type (WT) littermates.

Immunization with the 4 …

Replication-Competent, Tumor-Specific Immuno-Gene Vectors Allow For Exchange Of Transgenes And Lead To Viral Persistence Following Iv Administration, Lee S Rosen, Christian Ottensmeier, Maria Hawkins, Aung Naing, Guru Sonpavde, Brian A Van Tine, Eileen E Parkes, Sean M O'Cathail, Rui-Ru Ji, Matthew Thomas, Andrea Stacey, Maria Stella Sasso, Oliver Rosen

Faculty, Staff and Student Publications

Introduction: Enadenotucirev (EnAd) and successor transgene-armed Tumor-Specific Immuno-Gene (T-SIGn) vectors are replication-competent, blood-stable viral vectors that traffic to tumor sites following intravenous (IV) administration. Following initial proof of mechanism for this immunotherapy modality, there is a need to identify a safe dosing approach, understand whether transgenes affect tolerability, and determine how to measure exposure and pharmacodynamic effects.

Methods: Safety data from multiple phase 1 trials were aggregated to assess various dosing regimens and toxicities, including those that may be associated with transgene arming. Viral delivery to tumors, peripheral viral persistence, transgene expression, and cytokine responses were also assessed and compared …

Corrigendum To "Single-Cell Proteomic Analysis Reveals Multiple Myeloma Heterogeneity And The Dynamics Of The Tumor Immune Microenvironment In Precursor And Advanced States" [Neoplasia 66 (2025) 1101189], Mohamed Kamal, Stephanie N Shishido, Jeremy Mason, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

No abstract provided.

Diffuse Cutaneous Alk-Immunoreactive Histiocytosis With Mef2c::Flt3 Fusion, Sanjana Likki, Kevin Lee, Fiorinda Muhaj, Wei Wang, Pei Lin, Woo Cheal Cho, Doina Ivan, Carlos A Torres-Cabala, Luis Fayad, Jonathan L Curry

Faculty, Staff and Student Publications

No abstract provided.

Multi-Modal Spatial Characterization Of Tumor Immune Microenvironments Identifies Targetable Inflammatory Niches In Diffuse Large B Cell Lymphoma, Yibo Dai, Atish Kizhakeyil, Dai Chihara, Xubin Li, Yunhe Liu, Tania Patricia Sainz Zuniga, Ashley Wilson, Jared Henderson, Daniil Vibe, Arman Petrosyants, Connor Jacobson, Alexander Sarachakov, Krystle Nomie, Kirill Kryukov, Aleksander Bagaev, Ayushi Chauhan, Jason R Westin, Christopher R Flowers, Francisco Vega, Linghua Wang, Michael R Green

Faculty, Staff and Student Publications

Diffuse large B cell lymphomas (DLBCLs) are a heterogeneous group of malignancies that can arise in lymph nodes or extranodal locations, including immune-privileged sites. Here, we applied highly multiplexed spatial transcriptomics and proteomics together with genomic profiling to characterize the immune microenvironment architecture of 78 DLBCL tumors. We define seven distinct cellular niches, each characterized by unique cellular compositions, spatial organizations and patterns of intercellular communication associated with niche-specific phenotypes of both T cells and tumor B cells. Among these, DLBCLs from immune-privileged sites showed abundant T cell infiltration into diffuse niches, where immune cells were intermixed with tumor B …

Data-Driven Abdominal Phenotypes Of Type 2 Diabetes In Lean, Overweight, And Obese Cohorts From Computed Tomography, Lucas W Remedios, Chloe Cho, Trent M Schwartz, Dingjie Su, Gaurav Rudravaram, Chenyu Gao, Aravind R Krishnan, Adam M Saunders, Michael E Kim, Shunxing Bao, Alvin C Powers, Bennett A Landman, John Virostko

Faculty, Staff and Student Publications

Purpose: Although elevated body mass index (BMI) is a well-known risk factor for type 2 diabetes, the disease's presence in some lean adults and absence in others with obesity suggests that more detailed measurements of body composition may uncover abdominal phenotypes of type 2 diabetes. With artificial intelligence (AI) and computed tomography (CT), we can now leverage robust image segmentation to extract detailed measurements of size, shape, and tissue composition from abdominal organs, abdominal muscle, and abdominal fat depots in 3D clinical imaging at scale. This creates an opportunity to empirically define body composition signatures linked to type 2 diabetes …

Basal Cell Carcinoma Risk Prediction In Survivors Of Childhood Cancer, Cindy Im, Christina Boull, Zhe Lu, Kenneth Liao, Hasibul Hasan, Linwan Xu, Yadav Sapkota, Rebecca M Howell, Michael A Arnold, Miriam R Conces, Ashley J Housten, Judith Gebauer, Thorsten Langer, Jop C Teepen, Leontien C M Kremer, Louis S Constine, Yutaka Yasui, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Yan Yuan, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Survivors of childhood cancer face excess risk of developing basal cell carcinoma. Age-specific basal cell carcinoma risk prediction models for survivors may support targeted screening recommendations.

Methods: We developed models predicting basal cell carcinoma risk by ages 40 and 50 years featuring detailed cancer treatment predictors, utilizing statistical and machine-learning algorithms and data from 23 166 five-year survivors in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study. Selected models were externally validated in 5314 survivors in the St Jude Lifetime Cohort. Model discrimination and precision were evaluated using the area under the receiver operating characteristic curve (AUROC) …

Study Of 18 F-Fluciclovine Pet For Serial Assessment Of Glioblastoma Tumor Volumes During Surgery And Radiotherapy, Samir A Dagher, Jason M Johnson, Rania M M Mohamed, Shehbaz Ansari, Osama Mawlawi, Ho-Ling Liu, Max Wintermark, Dawid Schellingerhout, Lesley Flynt, Debra N Yeboa, Jeffrey S Weinberg, Sherise D Ferguson, Maria K Gule-Monroe

Faculty, Staff and Student Publications

PURPOSE: Recent evidence supports incorporating 18 F-Fluciclovine PET for glioblastoma treatment planning and monitoring, as it better captures tumor infiltration compared to conventional MRI. However, the relationship between PET- and MRI-defined tumor volumes remains unclear, particularly in the post-treatment setting. This study prospectively compares tumor volumes on MRI and PET at multiple timepoints throughout the treatment course and evaluates volumetric changes with therapy.

METHODS: We prospectively enrolled 8 adults with IDH-wildtype glioblastoma treated with surgery and chemoradiation between September 2019 and 2021. Participants underwent paired 18 F-Fluciclovine PET/CT and conventional MRI at four timepoints: preoperatively, pre-radiation, and at one- and …

B-Cell-Specific Wwox Deletion Promotes Plasmablastic Tumor Development And Proinflammatory Signatures In Myeloma Model, Tabish Hussain, Matthew D Bramble, Bin Liu, Martin C Abba, Marta Chesi, C Marcelo Aldaz

Faculty, Staff and Student Publications

Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk^∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk^∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic …