Jonathan A. Gutman

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.

Personal values research in marketing has recently received a substantial amount of attention from both academics and practitioners. This more in-depth profiling of the consumer and his or her relationship to products offers potential not only for understanding the “cognitive” positionings of current products but also permits the development of positioning strategies for new products. Endorsing this more psychological view of the marketplace, Sheth (1983) suggested that to be competitive in marketing products in the 1980s, both researchers and management are going to have to, if they have not already, adopt this consumerbased orientation rather than one that merely focuses on product characteristics.

Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front 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 profile, 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 findings, 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.