To practitioner and researcher alike, consumer values play an important role in understanding behavior in the marketplace. This paper presents a model linking perceived product attributes to values.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org. . American Marketing Association is collaborating with JSTOR to digitize, preserve and extend access to Journal of Marketing. A Means-End Chain Model Based on Consumer Categorization Processes To practitioner and researcher alike, consumer values play an important role in understanding behavior in the marketplace. This paper presents a model linking perceived product attributes to values. VALUES have been shown to be a powerful force in governing the behavior of individuals in all aspects of their lives (Rokeach 1968, Yankelovich 1981). Their use in marketing planning and strategy could be improved if the behavior of consumers could be related to their values. Several attempts have been made to provide a theoretical and conceptual structure connecting consumers' values to their behavior (Howard 1977, Vinson, Scott and Lamont 1977, Young and Feigin 1975). These attempts can be subsumed under the rubric of a means-end chain. Means are objects (products) or activities in which people engage (running, reading). Ends are valued states of being such as happiness, security, accomplishment. A means-end chain is a model that seeks to explain how a product or service selection facilitates the achievement of desired end states. Such a model consists of elements that represent the major consumer processes that link values to behavior.The means-end chain concept offers marketing managers a way to position products by associating means (the physical aspects of products) with advertising that seeks to tie the consumption of products to the achievement of desired ends (valued states). For example, knowing that consumers want to look well dressed doesn't tell us much unless we know why they want to look that way (sexual attractiveness, accomplishment, neatness, etc., which are value-level considerations) and what attributes in clothing they associate with being well dressed. For the means-end chain to have a central place in marketing planning and consumer research, the nature of the elements comprising means-end chains and the nature of the connections between these elements must be specified, and the model must be operationalized so as to facilitate research. Conceptual Model for Means-End ChainThe purpose of this paper is to present the author's means-end chain model. The model is based on two fundamental assumptions about consumer behavior:(1) that values, defined here as desirable end-states of existence, play a dominant role in guiding choice patterns, and (2) that people cope with the tremendous diversity of products that are potential satisfiers of their values by grouping them into sets or classes so as to reduce the complexity of choice. This suggests that in addition to the product-clas...

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Leukemia stem cells (LSCs) drive the initiation and perpetuation of AML, are quantifiably associated with worse clinical outcomes, and often persist after conventional chemotherapy resulting in relapse 1-5. In this report, we show that treatment of older AML patients with the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax in combination with azacitidine results in deep and durable remissions and is superior to conventional treatments. We hypothesized that these promising clinical results were due to targeting LSCs. Analysis of LSCs from patients undergoing treatment with venetoclax + azacitidine showed disruption of the TCA cycle manifested by decreased alpha-ketoglutarate and increased succinate levels, suggesting inhibition of electron transport chain complex II. In vitro modeling confirmed inhibition of complex II via reduced glutathionylation of succinate dehydrogenase. These metabolic perturbations suppress oxidative phosphorylation (OXPHOS), which efficiently and selectively targets LSCs. Our findings show for the first time that a therapeutic intervention can eradicate LSCs in AML patients by disrupting the metabolic machinery driving energy #

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Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, upfront resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we report that responses to venetoclax + azacitidine in patients with AML correlate closely with developmental stage, where phenotypically primitive AML is sensitive, but monocytic AML is more resistant. Mechanistically, resistant monocytic AML has a distinct transcriptomic profi le, loses expression of venetoclax target BCL2, and relies on MCL1 to mediate oxidative phosphorylation and survival. This differential sensitivity drives a selective process in patients which favors the outgrowth of monocytic subpopulations at relapse. Based on these fi ndings, we conclude that resistance to venetoclax + azacitidine can arise due to biological properties intrinsic to monocytic differentiation. We propose that optimal AML therapies should be designed so as to independently target AML subclones that may arise at differing stages of pathogenesis. SIGNIFICANCE: Identifying characteristics of patients who respond poorly to venetoclax-based therapy and devising alternative therapeutic strategies for such patients are important topics in AML. We show that venetoclax resistance can arise due to intrinsic molecular/metabolic properties of monocytic AML cells and that such properties can potentially be targeted with alternative strategies.

Given the limited treatment options for relapsed lymphoma post-allogeneic hematopoietic cell transplantation (post-allo-HCT) and the success of programmed death 1 (PD-1) blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label after allo-HCT. To characterize the safety and efficacy of PD-1 blockade in this setting, we conducted a multicenter retrospective analysis of 31 lymphoma patients receiving anti-PD-1 mAbs for relapse post-allo-HCT. Twenty-nine (94%) patients had cHL and 27 had ≥1 salvage therapy post-allo-HCT and prior to anti-PD-1 treatment. Median follow-up was 428 days (range, 133-833) after the first dose of anti-PD-1. Overall response rate was 77% (15 complete responses and 8 partial responses) in 30 evaluable patients. At last follow-up, 11 of 31 patients progressed and 21 of 31 (68%) remain alive, with 8 (26%) deaths related to new-onset graft-versus-host disease (GVHD) after anti-PD-1. Seventeen (55%) patients developed treatment-emergent GVHD after initiation of anti-PD-1 (6 acute, 4 overlap, and 7 chronic), with onset after a median of 1, 2, and 2 doses, respectively. GVHD severity was grade III-IV acute or severe chronic in 9 patients. Only 2 of these 17 patients achieved complete response to GVHD treatment, and 14 of 17 required ≥2 systemic therapies. In conclusion, PD-1 blockade in relapsed cHL allo-HCT patients appears to be highly efficacious but frequently complicated by rapid onset of severe and treatment-refractory GVHD. PD-1 blockade post-allo-HCT should be studied further but cannot be recommended for routine use outside of a clinical trial.

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We investigated the potential role of an immune reaction in mediating the dominant engraftment of 1 cord blood unit in 14 patients who received a double-unit cord blood transplantation (CBT). In 10 patients, dominant engraftment of a single donor unit emerged by day 28 after CBT. In 9 of these 10 patients, a significant subset of CD8 ؉ CD45RO ؉/؊ CCR7 ؊ T cells, present in peripheral blood mononuclear cells and derived from the engrafting cord blood unit, produced interferon-␥ (IFN-␥) in response to the nonengrafting unit. No significant population of IFN-␥-secreting cells was detectable when posttransplantation peripheral blood mononuclear cells were stimulated against cells from the engrafted unit (P < .001) or from a random human leukocyte antigen disparate third party (P ‫؍‬ .003). Three patients maintained persistent mixed chimerism after CBT, and no significant IFN-␥-secreting cells were detected after similar stimulations in these patients (P < .005). Our data provide the first direct evidence in human double-unit CBT recipients that immune rejection mediated by effector CD8 ؉ T cells developing after CBT from naive precursors is responsible for the failure of 1 unit to engraft. Future investigations based on these findings may result in strategies to predict a dominant unit and enhance graft-versus-leukemia effect. (Blood. 2010;115:757-765)