Search

Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study.

Chimeric antigen receptor (CAR) T-cell therapy has altered the treatment of lymphoid malignancies, but it is associated with acute toxicities and so-called “on-target, off-tumor” effects that place patients at risk for infectious complications. Respiratory viral infections (RVIs) are a common, but poorly characterized complication of CAR T-cell therapy.

Background:Treatment options for elderly unfit/frail (U/F) patients (pts) with diffuse large B-cell lymphoma (DLBCL) are often limited due to comorbidities or functional decline. Less toxic, efficacious alternatives to full-dose chemoimmunotherapy (CIT) are needed. Mosunetuzumab (Mosun) is a first-in-class CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells. Mosun monotherapy has demonstrated efficacy, durable complete responses (CR), and manageable safety in U/F pts with untreated DLBCL (NCT03677154; Olszewski et al. ASH 2022). Subgroup analysis from an ongoing Phase Ib/II study (NCT03671018) of Mosun plus polatuzumab vedotin (Pola; M-Pola) in pts with relapsed/refractory DLBCL demonstrated efficacy and a manageable safety profile in pts ≥65 years (yrs) (Olszewski et al. ASH 2022). We report preliminary efficacy and safety data from the M-Pola cohort of study NCT03677154 in elderly U/F pts with newly diagnosed DLBCL.

Background:Richter transformation (RT) occurs in up to 10% of patients with chronic lymphocytic leukemia (CLL), typically presents as an aggressive diffuse large B-cell lymphoma (DLBCL) and is associated with poor survival. RT has no approved standard therapy; and clinical trial enrollment is the preferred first line of therapy. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, that inhibits both wildtype and C481-mutant BTK with equal low nM potency, has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval. Pirtobrutinib demonstrated durable overall response rates (ORR) and was well tolerated in patients (pts) with poor-prognosis B-cell malignancies regardless of prior therapy. Here we provide updated safety and efficacy of pirtobrutinib in RT pts from the phase 1/2 BRUIN trial (NCT03740529).

Olszewski: Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding. Avigdor:Takeda, Gilead, Pfizer: Consultancy, Honoraria; Janssen, BMS: Research Funding. Babu:Amgen: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Sanofi: Research Funding; Janssen Oncology: Research Funding; Lutheran Hospital: Other; Bayer: Honoraria; AstraZeneca: Consultancy, Honoraria; AstraZeneca/MedImmune: Research Funding; Boehringer Ingelheim: Consultancy; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Argenx: Consultancy, Research Funding; Novartis: Research Funding; Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Syndax: Research Funding; Nektar: Research Funding; Merck: Research Funding; AbbVie: Research Funding; TG Therapeutics: Research Funding. Levi:Abbvie Inc: Consultancy, Research Funding. Abadi:Abbvie Inc: Research Funding; Roche, Gilead, Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Holmes:Texas Oncology PA: Current Employment; Gilead/Kite, Celgene/Juno, Rigel, Karyopharm, Janssen, Dova: Consultancy; Gilead/Kite, Novartis, Autolus, Celgene/Juno/bluebird, Genentech, Inc., Rigel, Janssen, Unum, ADC Therapeutics, Seattle Genetics, Incyte, Verastem: Research Funding; Kite, Karyopharm, Seattle Genetics, Rigel, Dova: Speakers Bureau. McKinney:UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Inc., Celgene: Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene: Consultancy. McCord:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Xie:F. Hoffmann-La Roche: Current Employment. Chen:Janssen Pharmaceuticals: Current equity holder in publicly-traded company; Bristol-Myer Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Sarouei:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Qayum:F. Hoffmann-La Roche: Current Employment. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Sellam:F. Hoffmann-La Roche: Current Employment. Eradat:UCLA Medical Center, David Geffen school of Medicine at UCLA: Current Employment; Genentech, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; F. Hoffmann-La Roche: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astrazeneca, Atara, Kite, Juno, Acerta, BeiGene, Celgene: Research Funding.Mosunetuzumab (RG7828; CD20-TDB) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.

The article focuses on the questions raised to Donald Trump Administration’s initial approach on the role of public participation and intergovernmental coordination in federal land management. It mentions the part of federal land policy to both Democratic and Republican presidential political party platforms in 2016. It cites that public lands exemplify democracy in two ways which include allowing all Americans in the decision making processes and allowing equal access to federal lands.

Temperature plays an important role in the growth and development of insects, and the temperature at which an insect develops can affect both behavior and reproduction in adult insects. This study was conducted to determine the effects of temperature on development and survival in the egg and larval stages of Osmia cornifronsRadozskowski (Hymenoptera: Megachilidae) over a broad range of temperatures. O. cornifronsindividuals were placed in environmental chambers at 5, 13, 21, 29, 37, and 45 °C and their development was tracked daily. Developmental data was modelled using the Briére function and simulated by incorporating the developed model and Weibull function. Models were validated with developmental data from randomly selected bees at sites in Morgantown (n = 28) and Kearneysville (n = 78), West Virginia, USA. Osmia cornifronseggs survived at 13, 21, and 29 °C, but were unable to survive at other temperatures. Larvae survived at 21 and 29 °C, with 88.5 and 45.5% survival, respectively. The thermal window for the development of egg and 1st instar was 17.99 °C, and for 2nd instar to prepupa was 12.58 °C. Nearly all validation data fell within the 95% prediction interval, indicating that the models accurately represented the thermal biology of O. cornifronsin field. The narrow thermal window found in this study for O. cornifronslarval development indicates that O. cornifronsis sensitive to temperature change during this life history stage. Implications of the thermal requirements of O. cornifronsfor propagation and management are discussed.

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1. We also identified mutations in KRAS, TP53, and TERT. Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre+ GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro. We also found that GNA13-deficient mice have increased numbers of GC B cells that display impaired caspase-mediated cell death and increased frequency of somatic hypermutation in the immunoglobulin VH locus. Lastly, GNA13 deficiency, combined with conditional MYC transgene expression in mouse GC B cells, promotes lymphomagenesis. Thus, GNA13 loss is associated with GC B-cell persistence, in which impaired apoptosis and ongoing somatic hypermutation may lead to an increased risk of lymphoma development.

The American West is defined first and foremost by aridity, scarcity, and variability of water resources. In response to this geographic imperative, the region has evolved a robust menu of legal, institutional, and community-based approaches to managing water and conflicts at local, state, and national levels. While far from perfect, this framework may offer lessons to other regions throughout the world that are increasingly faced with water conflicts due to scarcity and variability of water resources. The resulting menu of approaches reflects an adaptive, collaborative, and nested system of governing water resources. [ABSTRACT FROM AUTHOR]

No abstract.

Background:Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (NHL). Although most patients with FL respond well to first-line therapy, they will inevitably relapse, and the subsequent course is often characterized by a pattern of recurrent relapses with progressively shorter intervals between treatment lines. Moreover, the use of multiple consecutive therapies often leads to refractory disease with severely limited treatment options, demonstrating the need for new therapies for this patient population. Currently approved phosphoinositide 3-kinase (PI3K) inhibitors are often poorly tolerated. Parsaclisib, a potent, highly-selective, next-generation PI3Kδ inhibitor, has shown promising activity in patients with previously treated B-cell malignancies. Here, we report preliminary results of CITADEL-203 (NCT03126019), a multicenter, open-label phase 2 study of parsaclisib in relapsed or refractory (R/R) FL.

Background: Allogeneic hematopoietic transplantation (HCT) is frequently considered for patients (pts) with relapsed T-cell lymphoma (TCL) and less often as consolidation of initial therapy. Outcomes from prior registry data show that only 31% of pts remain disease free 3 years after HCT (Smith et al. JCO 2013). However, several single institution studies have superior outcomes. We previously presented an analysis of allogeneic transplant in T-cell lymphoma but have expanded this effort to 12 academic centers with longer follow up (Mehta-Shah ASH 2017).

Background:Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL) in Western countries, accounting for 20-30% of all NHLs (Hübel K. Hemasphere.2020;4:e317). While most patients (pts) respond well to first-line therapy, they typically experience frequent relapses and progressively shorter duration of response with subsequent lines of therapy (Batlevi CL. Blood Cancer J.2020;10:74; Rivas-Delgado A. Br J Haematol.2019;184:753-9), and increasingly refractory disease with limited treatment options. Thus, there is an unmet need for effective treatment options for pts with relapsed or refractory (R/R) FL. Parsaclisib is a potent, highly selective, next-generation phosphatidylinositol 3-kinase (PI3K)δ inhibitor. Here we report results of the primary analysis of CITADEL-203 (NCT03126019, EudraCT 2017-001624-22), a phase 2, multicenter, open-label study of parsaclisib monotherapy in R/R FL.

Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rare non-Hodgkin lymphoma subtype that occurs predominantly in young adults, with an overall favorable prognosis. The cell of origin is presumed to be thymic medullary B-cells and the gene expression profile of PMBL is similar to classic Hodgkin lymphoma. Recent studies have begun unravelling the genomic alterations underlying PMBL. Frequent, recurrent mutations (e.g. B2M, TNFAIP3, SOCS1, STAT6, GNA13) have been reported, but most of the studies have analyzed a small number of cases. To gain further insights into disease biology, we recruited 63 cases of PMBL as part of the Atlas of Blood Cancer Genomes (ABC-G) initiative, a consortium consisting of 25 institutions.

Introduction

In a survey of SAF-accredited natural resources schools, 36 of 40 educators said natural resource professionals need more training in public involvement and dispute resolution, and 96 percent of respondents said such training was important" or "essential." Despite budgetary and staff constraints, the number of SAF-accredited schools offering specific courses in these topics has grown dramatically, from a reported three in 1992 to 15 in 1997. At most schools, these topics also have been incorporated into already-required courses on policy, planning, and management. The authors describe a model course in public involvement and conflict resolution and list resources for educators.

Public involvement in water resources planning is traditionally limited. While decision makers may solicit public input, affected parties rarely have the opportunity to participate directly in the decision-making process. In recent years, this lack of meaningful public participation has been exacerbated by an increase in the number of individuals and groups interested in water management. In light of these limitations in and new demands on water resource planning, there has been a loud call for the development of new mechanisms to enhance public involvement and conflict management. The state of Montana has responded to this call by developing a state water plan through a collaborative, consensus-building process that directly involves the public in water policy decisions. In general, the process is based on the principles of environmental dispute resolution. After reviewing these principles, the design and implementation of Montana's state water plan is examined. The advantages and limitations of this collaborative, consensus-building process are outlined, along with the conditions necessary for successful implementation.

Burnett: Molecular Templates, Inc.: Employment. Strack:Molecular Templates, Inc.: Employment. Lehner:Molecular Templates, Inc.: Employment. Higgins:Molecular Templates, Inc.: Employment, Equity Ownership. Katz:Dova: Consultancy; Stemline: Speakers Bureau.

Erba: Amgen, Celgene, Daiichi Sankyo, ImmunoGen, Incyte, Jazz Pharmaceuticals, Millennium, Novartis, Ono, Pfizer, Seattle Genetics, Sunesis: Consultancy; Celgene, Incyte, Novartis: Speakers Bureau; Agios, Amgen, Astellas Pharma, Daiichi Sankyo, ImmunoGen, Janssen, Jazz Pharmaceuticals, Juno, Millennium, Seattle Genetics: Research Funding.

Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.

Munoz: Pharmacyclics /Janssen: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene/Juno: Consultancy, Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy; Alexion: Consultancy; Portola: Research Funding; Incyte: Research Funding; Bayer: Consultancy, Speakers Bureau; Merck: Consultancy. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Unum Therapeutics Inc.: Research Funding; Juno: Consultancy, Other: advisory board. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Stiff:Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding. Sachs:Unum Therapeutics Inc.: Employment. Ranger:Unum Therapeutics Inc.: Employment. Harris:Unum Therapeutics Inc.: Employment. Payumo:Unum Therapeutics Inc.: Employment. Akard:Bristol-Myers Squibb: Speakers Bureau; Gilead: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Celgene: Speakers Bureau.

No relevant conflicts of interest to declare.

Introduction: Outcomes of acute myeloid leukemia (AML) in older patients remain unsatisfactory with low rates of complete remission (CR), disease-free survival (DFS), and overall survival (OS). Microtransplantation - in which allogeneic cells are infused without substantial engraftment (<2% donor cell engraftment) - has the potential to improve anti-tumor immunity without the risks of allogeneic hematopoietic stem cell transplant and graft-vs-host disease (GVHD).

Background: Autologous T cells engineered to express the universal ACTR chimeric receptor kill tumors through interactions with tumor-targeting antibodies [Kudo, Cancer Res. 2014]. Preclinical findings with ACTR+ T cells, which bind immunoglobulin Fc via CD16V158 and signal via CD3ζ and 4-1BB (ACTR087), demonstrate markedly enhanced target- and antibody-specific tumor cell cytotoxicity, as evidenced by CD20+ B cell lymphoma killing in combination with rituximab, compared with rituximab alone. Preclinical data also demonstrate rituximab dose-dependent effects in combination with ACTR087, suggesting that the therapeutic index of ACTR087 in combination with rituximab may be affected by rituximab dose or schedule and present an advantage over chimeric antigen receptor (CAR) T cell therapies [Huet H, Blood 2016]. Study UT-201501 (ATTCK-20-2) is the first clinical trial of ACTR087 in combination with rituximab in patients with relapsed or refractory CD20+ B cell lymphoma previously treated with rituximab (NCT02776813). We report data from the 7 patients treated with ACTR087 in the first dose level of the ATTCK-20-2 study.

No relevant conflicts of interest to declare.

The article discusses ownership in a business in a limited liability firm and incorporation including valuing of ownership in the business by court, end of business partnership and discount on the value of the minority owners' interest.

The article provides an answer of a question on data security strategies implemented by business to protect its future.

The article discusses items to consider in dealing with fundamental business law issues to prepare an organization for 2015, and mentions topics including the importance of changing the legal structure of a business, securing authority for transactions, and complying with corporate formalities.

No relevant conflicts of interest to declare.

The article offers information on intellectual property which refers to patents, copyrights and trademarks, and outlines the importance of intellectual property to business including protection of original works of authorship.

Wnt signaling is a highly conserved pathway with diverse roles in proliferation, self-renewal and differentiation in multiple tissue types. Aberrant Wnt signaling and deletions/mutations of Wnt regulatory genes have been found in a variety of malignancies including lymphoma. The factors which govern this pathway and the precise role of Wnt signaling in mediating tumor proliferation are unknown. We previously identified recurrent mutations in Wnt pathway genes including APC and WIF1 in diffuse large B cell lymphoma (DLBCL) using exome sequencing and thus sought to investigate if targeting of Wnt with molecular agents would be a viable treatment approach in NHL.Alamar blue proliferation assays were used to determine IC50 values for 2 small molecule inhibitors of Wnt signaling: ICG001 (a selective inhibitor of TCF/LEF1 mediated transcription) and salinomycin (an ionophore which has been shown to target Wnt) in a panel of 65 cell lines comprising subtypes of lymphoma (including 7 ABC DLBCL, 16 GCB DLBCL, 10 Burkitt lymphoma, 5 mantle cell lymphoma and 5 primary effusion lymphoma cell lines) and leukemia. Both molecules inhibited proliferation of cell lines in the screening panel at physiologically achievable concentrations (IC50 range for salinomycin 0.11–6.23 μM, IC50 range for ICG001 0.96–28.9 μM). IC50s values for salinomycin and ICG001 correlated well (Pearson r=0.56) suggesting a common mechanism of action between the 2 agents. Furthermore, we found lower IC50 values in primary effusion lymphoma (PEL) cell lines (0.35 μM vs. 1.37 μM for other cell line histologies, p=0.01 for salinomycin and 3.25 μM vs. 6.22 μM, p=0.13 for ICG001), which is a lymphoma subtype associated with aberrant Wnt signaling. We did not note significant differences in cytoxicity among other subsets. Wnt activity was confirmed using TOPFLASH luciferase assays and correlated with sensitivity to ICG001 and salinomycin.We then used gene expression profiles derived from Affymetrix Gene 1.0 arrays from each cell line and a Cox proportional hazards model to identify genes associated with sensitivity or resistance to both agents. A gene list consisting of 367 genes associated with either sensitivity or resistance at p<0.05 for both agents was derived from this analysis. Hierarchical clustering was used to define 2 groups of cell lines based upon these genes and analyzed with gene set enrichment (GSEA). GSEA comparisons of sensitive and resistance groups derived from this method revealed that genes associated with mitochondrial pathways were highly associated with response to both ICG001 and salinomycin (FDR=0.036, p=0.03).Specifically, expression of genes involved in glycolysis and mitochondrial respiration including FBG1, CS, UBQRB5, OXA1L, LDHA and ATP5B was higher in ICG001 and salinomycin-sensitive cell lines. Conversely, we noted higher IC50s in cell lines with higher expression of mitochondrial genes having opposing functions, including PC and CPT1A. This overall suggests that tumor cells utilizing glycolytic and oxidative pathways are sensitive to Wnt inhibition. Remarkably, the GCB DLBCL cell line Pfeiffer also was noted to contain an inactivating mutation in APC and had the lowest noted IC50 among DLBCL cell lines.The Wnt pathway appears an important oncologic driver in at least a subset of NHLs and we found ICG001 and salinomycin have significant in vitro activity in NHLs. These agents may be most useful in subsets of tumors with high mitochondrial mass and/or oxidative phosphorylation. This work serves as a starting point to characterize the importance of the Wnt pathway in NHL and identifies inhibition of this pathway as a therapeutic opportunity in lymphomas.No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.