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Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

In Vitro Methods For Generating Highly Purified Ebv Associated Tumor Antigen-Specific T Cells By Using Solid Phase T Cell Selection System For Immunotherapy, Jongming Li, Bijoyesh Mookerjee, John Wagner, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Adoptive cell transfer immunotherapy has been utilized to treat EBV related human malignancies including post-transplant lymphoproliferative diseases, Hodgkin's lymphoma and nasopharyngeal carcinoma. However, there are limited options available for tumor antigen-specific T cell purification. Here we describe a novel solid phase T cell selection system, in which monocytes or EBV transformed B-lymphocytes are immobilized on solid support for antigen-specific T cell purification. We hypothesize and prove that antigen-specific T cells recognize their cognate antigens and bind to them faster than non-antigen specific T cells. Therefore antigen-specific T cells can be concentrated on the surface after removing the non-adherent cells by …

Induction Of Insulin Secretion In Engineered Liver Cells By Nitric Oxide, Latha Muniappan, Sabire Özcan

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs …

Nicotinamide Riboside Kinase Structures Reveal New Pathways To Nad+, Wolfram Tempel, Wael M. Rabeh, Katrina L. Bogan, Peter Belenky, Marzena Wojcik, Heather F. Seidle, Lyudmila Nedyalkova, Tianle Yang, Anthony A. Sauve, Hee-Won Park, Charles Brenner

Dartmouth Scholarship

The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize …

Regulation Of Mucin Gene Expression By Creb Via A Nonclassical Retinoic Acid Signaling Pathway, Seung-Wook Kim, Jeong Soo Hong, Seung-Hee Ryu, Wen-Cheng Chung, Joo-Heon Yoon, Ja Seok Koo

Faculty, Staff and Student Publications

Vitamin A and its metabolite retinoic acid (RA) are essential elements for normal lung development and the differentiation of lung epithelial cells. We previously showed that RA rapidly activated cyclic AMP response element-binding protein (CREB) in a nonclassical manner in normal human tracheobronchial epithelial (NHTBE) cells. In the present study, we further demonstrated that this nonclassical signaling of RA on the activation of CREB plays a critical role in regulating the expression of airway epithelial cell differentiation markers, the MUC2, MUC5AC, and MUC5B genes. We found that RA rapidly activates the protein kinase Calpha isozyme and transmits the activation signal …

Selective Repression Of Retinoic Acid Target Genes By Rip140 During Induced Tumor Cell Differentiation Of Pluripotent Human Embryonal Carcinoma Cells, Kelly C. Heim, Kristina A. White, Dexin Deng, Craig R. Tomlinson, Jason Moore, Sarah Freemantle, Michael Spinella

Dartmouth Scholarship

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification …

Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal

Department of Pediatrics Faculty Papers

Phosphatidylserine (PS)-positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1alpha, TNF-alpha, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface-expressed PS (PSR) similar to that expressed on activated macrophages. …

Evaluating The Effectiveness Of Psychosocial Interventions For Individuals With Visible Differences: A Systematic Review Of The Empirical Literature., Alyson Bessell, Timothy P. Moss

More Faculty of Health Research

The objective of this review was to systematically identify and evaluate all known studies testing empirically the efficacy of psychosocial intervention programmes for adults with visible differences. Twelve papers met the inclusion criteria. None of the papers demonstrated adequately the clinical effectiveness of the interventions. The review concluded that further research was needed to demonstrate adequately the effectiveness of existing interventions, and a greater number of Randomised Controlled Trials and experimental studies were required to increase the methodological validity of intervention studies.

Human Muc4 Mucin Induces Ultra-Structural Changes And Tumorigenicity In Pancreatic Cancer Cells., N. Moniaux, P. Chaturvedi, G. C. Varshney, Jane L. Meza, J. F. Rodriguez-Sierra, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is …

American Academy Of Allergy, Asthma & Immunology Work Group Report: Allergy Diagnosis In Clinical Practice, Dana V. Wallace, Sami L. Bahna, Stan Goldstein, Robert G. Hamilton, John R. Cohn

Department of Medicine Faculty Papers

No abstract provided.

Gangliocytic Paraganglioma: Case Report And Review Of The Literature, Agnes Witkiewicz, Avi Galler, Charles Yeo

Department of Surgery Faculty Papers

Gangliocytic paraganglioma is a rare tumor, which occurs nearly exclusively in the second portion of the duodenum. Generally, this tumor has a benign clinical course, although rarely, it may recur or metastasize to regional lymph nodes. Only one case with distant metastasis has been reported. We present a case of duodenal gangliocytic paraganglioma treated first by local resection followed by pylorus-preserving pancreaticoduodenectomy. Examination of the first specimen revealed focal nuclear pleomorphism and mitotic activity, in addition to the presence of three characteristic histologic components: epithelioid, ganglion, and spindle cell. In the subsequent pancreaticoduodenectomy specimen, there was no residual tumor identified …

Navigating The Us Health Care System: A Video Guide For Immigrant And Diverse Populations., Alison M Bobal, Heather L Brown, Teresa L Hartman, Marty Magee, Cynthia M Schmidt

Journal Articles: Leon S. McGoogan Health Sciences Library

No abstract provided.

Azithromycin In The Extremely Low Birth Weight Infant For The Prevention Of Bronchopulmonary Dysplasia: A Pilot Study, Hubert O. Ballard, Michael I. Anstead, Lori A. Shook

Pediatrics Faculty Publications

BACKGROUND: Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (< or = 1000 grams) population.

METHODS: Infants < or = 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.

RESULTS: A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and …

The Flagellum Of Pseudomonas Aeruginosa Is Required For Resistance To Clearance By Surfactant Protein A, Shiping Zhang, Francis X. Mccormack, Roger C. Levesque, George A. O'Toole, Gee W. Lau

Dartmouth Scholarship

Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa …

The Pseudomonas Aeruginosa Secreted Protein Pa2934 Decreases Apical Membrane Expression Of The Cystic Fibrosis Transmembrane Conductance Regulator, Daniel P. Maceachran, Siying Ye, Jennifer M. Bomberger, Deborah A. Hogan, Agnieszka Swiatecka-Urban, Bruce Stanton, George A. O'Toole

Dartmouth Scholarship

We previously reported that Pseudomonas aeruginosa PA14 secretes a protein that can reduce the apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Here we report that we have used a proteomic approach to identify this secreted protein as PA2934 [corrected], and we have named the gene cif, for CFTR inhibitory factor. We demonstrate that Cif is a secreted protein and is found associated with outer membrane-derived vesicles. Expression of Cif in Escherichia coli and purification of the C-terminal six-His-tagged Cif protein showed that Cif is necessary and sufficient to mediate the reduction in apical membrane expression …

Efficacy Of The De Novo-Derived Antimicrobial Peptide Wlbu2 Against Oral Bacteria, Karen F. Novak, William J. Diamond, Sreenatha S. Kirakodu, Rebecca Peyyala, Kimberly W. Anderson, Ronald C. Montelaro, Timothy A. Mietzner

Center for Oral Health Research Faculty Publications

The efficacy of a novel synthetic antimicrobial peptide (WLBU2) was evaluated against three oral microorganisms (grown planktonically): Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. WLBU2 killed all three species, with F. nucleatum being the most susceptible. WLBU2 also reduced the bacterial burden of S. gordonii and F. nucleatum biofilms.

Bridging The Critical Chasm Between Service And Research: The Cancer Information Service’S Collaboratory, Linda Squiers, Nigel Bush, Robin C. Vanderpool, Ludmila Cofta-Woerpel, Cecilia Fabrizio

Health, Behavior & Society Faculty Publications

As a collaboratory for cancer communication and education research, the National Cancer Institute's (NCIs) Cancer Information Service (CIS) is in an ideal position to bridge the critical chasm that exists between service and research. This article describes the CIS' current research program as well as the CIS Research Agenda launched in 2005. The CIS' progress in developing and supporting recently funded studies that address this agenda is detailed. The unique resources and opportunities available to researchers, public health practitioners, health care providers, and community-based organizations interested in developing collaborative cancer communication and cancer education studies with the CIS are identified …

Phase I And Phase Ii Ocular Metabolic Activities And The Role Of Metabolism In Ophthalmic Prodrug And Codrug Design And Delivery, Abeer M. Al-Ghananeem, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

While the mammalian eye is seldom considered an organ of drug metabolism, the capacity for biotransformation is present. Compared to the liver, the metabolic capabilities of the eye are minuscule; however, phase I and phase II metabolic activities have been detected in various ocular structures. The careful consideration of ocular tissue metabolic processes within the eye has important implications for controlling the detoxification of therapeutic agents and for providing the potential for site-specific bio-activation of certain drug molecules, thus enabling significant improvements in drug efficacy and the minimization of side-effect from either local or systemic drug delivery to the eye. …

Oocyte Cytoplasmic Maturation: A Key Mediator Of Oocyte And Embryo Developmental Competence., A J Watson

Obstetrics & Gynaecology Publications

Efforts have intensified to successfully mature and inseminate oocytes in vitro and then culture ensuing embryos to transferable stages from a large number of mammalian species. Success varies, but generally even for the most successful species it is only possible to obtain a maximum of a 40 to 50% development of zygotes to the blastocyst stage. Reduced oocyte developmental competence is suggested as a primary reason for the reduced potential of in vitro-produced embryos. The vast majority of in vitro-matured oocytes are meiotically competent; however, many do not attain an optimal oocyte diameter before insemination. Variations in oocyte in vitro …

Impact Of Morbid Obesity On Outcome Of Laparoscopic Splenectomy., Edward P Dominguez, Yong U Choi, Bradford G Scott, Alan M. Yahanda Md, Facs, Edward A Graviss, John F Sweeney

PCI Publications and Projects

BACKGROUND: Because of the obesity epidemic, surgeons are operating on morbidly obese patients in increasing numbers. The aim of this study was to evaluate the impact of morbid obesity on the outcome of laparoscopic splenectomy.

METHODS: The study group consisted of 120 consecutive patients who underwent laparoscopic splenectomy for benign and malignant disease from March 1996 to May 2005. These patients were retrospectively divided into three groups. Group 1 had a body mass index (BMI) < 30. Group 2 patients had a BMI > or = 30 and < 40 and were considered obese. Group 3 had a BMI > or = 40 and were considered morbidly obese. Data including surgical approach (laparoscopic vs. hand-assisted), operative time, conversion rate, estimated blood …

Improving Student Dentist Competencies And Perception Of Difficulty In Delivering Care To Children With Developmental Disabilities Using A Virtual Patient Module, Harold L. Kleinert, Carla Sanders, John Mink, David A. Nash, Jeff Johnson, Sara Boyd, Sandra Challman

Human Development Institute Faculty Publications

An interactive, multimedia, virtual patient module was designed and developed on compact disc (CD-ROM) to address the need for student dentists to increase their competence and decrease their perception of difficulty in caring for children with developmental disabilities. A development team consisting of pediatric dentistry faculty members, parents of children with developmental disabilities, an individual with a developmental disability, and educational specialists developed an interactive virtual patient case. The case involved a ten-year-old child with Down syndrome presenting with a painful tooth. Student dentists were required to make decisions regarding proper interactions with the child, as well as appropriate clinical …

A Non-Pharmacological Intervention To Manage Behavioral And Psychological Symptoms Of Dementia And Reduce Caregiver Distress: Design And Methods Of Project Act3., Laura N Gitlin, Laraine Winter, Marie P Dennis, Walter W Hauck

Center for Applied Research on Aging and Health Research Papers

Project ACT is a randomized controlled trial designed to test the effectiveness of a non-pharmacological home-based intervention to reduce behavioral and psychological symptoms of dementia (BPSD) and caregiver distress. The study targets 272 stressed racially diverse family caregivers providing in-home care to persons with moderate stage dementia with one or more behavioral disturbances. All participants are interviewed at baseline, 4-months (main trial endpoint), and 6-months (maintenance). The four-month intervention involves up to 13 visits from an occupational therapist who works with families to problem-solve potential triggers (communication style, environmental clutter) contributing to behaviors, and instruct in strategies to reduce caregiver …

Repression Of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (Trail) But Not Its Receptors During Oral Cancer Progression, Nadarajah Vigneswaran, Darryl C. Baucum, Jean Wu, Yahuan Lou, Jerry Bouquot, Susan Muller, Wolfgang Zacharias

Faculty, Staff and Student Publications

BACKGROUND: TRAIL plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and thus has great therapeutic potential for cancer treatment. TRAIL binds to two cell-death-inducing (DR4 and DR5) and two decoy (DcR1, and DcR2) receptors. Here, we compare the expression levels of TRAIL and its receptors in normal oral mucosa (NOM), oral premalignancies (OPM), and primary and metastatic oral squamous cell carcinomas (OSCC) in order to characterize the changes in their expression patterns during OSCC initiation and progression. METHODS: DNA microarray, immunoblotting and immunohistochemical analyses were used to …

Glycosylation Regulates Turnover Of Cyclooxygenase-2., Mary B. Sevigny, Chai-Fei Li, Monika Alas, Millie Hughes-Fulford

Natural Sciences and Mathematics | Faculty Scholarship

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). COX-2 exists as 72 and 74kDa glycoforms, the latter resulting from an additional oligosaccharide chain at residue Asn(580). In this study, Asn(580) was mutated to determine the biological significance of this variable glycosylation. COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 protein and have five times greater COX-2 activity than cells expressing both glycoforms. Thus, COX-2 turnover appears to depend upon glycosylation of the 72kDa glycoform.

Bovine Immune Response To Shiga-Toxigenic Escherichia Coli O157:H7., Mark A Hoffman, Christian Menge, Thomas A Casey, William Laegreid, Brad T Bosworth, Evelyn A Dean-Nystrom

Manuscripts, Articles, Book Chapters and Other Papers

Although cattle develop humoral immune responses to Shiga-toxigenic (Stx+) Escherichia coli O157:H7, infections often result in long-term shedding of these human pathogenic bacteria. The objective of this study was to compare humoral and cellular immune responses to Stx+ and Stx- E. coli O157:H7. Three groups of calves were inoculated intrarumenally, twice in a 3-week interval, with different strains of E. coli: a Stx2-producing E. coli O157:H7 strain (Stx2+ O157), a Shiga toxin-negative E. coli O157:H7 strain (Stx- O157), or a nonpathogenic E. coli strain (control). Fecal shedding of Stx2+ O157 was significantly higher than that of Stx- O157 or the …

Guidelines And Standards For Performance Of A Pediatric Echocardiogram: A Report From The Task Force Of The Pediatric Council Of The American Society Of Echocardiography., Wyman W. Lai, Tal Geva, Girish S. Shirali, Peter C. Frommelt, Richard A. Humes, Michael M. Brook, Ricardo H. Pignatelli, Jack Rychik, Pediatric Council Of The American Society Of Echocardiography

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Androgen-Regulated Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Shalini Mitra, Lakshmanan Annamalai, Souvik Chakraborty, Kristen E. Johnson, Xiao-Hong Song, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate …

Insights Into Transcription Enhancer Factor 1 (Tef-1) Activity From The Solution Structure Of The Tea Domain, Asokan Anbanandam, Diana C Albarado, Catherine T Nguyen, Georg Halder, Xiaolian Gao, Sudha Veeraraghavan

Faculty, Staff and Student Publications

Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. …

Vulnerability Of Pathogenic Biofilms To Micavibrio Aeruginosavorus, Daniel Kadouri, Nel C. Venzon, George A. O'Toole

Dartmouth Scholarship

The host specificity of the gram-negative exoparasitic predatory bacterium Micavibrio aeruginosavorus was examined. M. aeruginosavorus preyed on Pseudomonas aeruginosa, as previously reported, as well as Burkholderia cepacia, Klebsiella pneumoniae, and numerous clinical isolates of these species. In a static assay, a reduction in biofilm biomass was observed as early as 3 hours after exposure to M. aeruginosavorus, and an ∼100-fold reduction in biofilm cell viability was detected following a a 24-h exposure to the predator. We observed that an initial titer of Micavibrio as low as 10 PFU/well or a time of exposure to the predator as short as 30 …

Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst

Dartmouth Scholarship

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …