Browsing by Author "Bergsagel, P. Leif"

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    Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes
    (Springer, 2022-06-15) Bustoros, Mark; Anand, Shankara; Sklavenitis-Pistofidis, Romanos; Redd, Robert; Boyle, Eileen M.; Zhitomirsky, Benny; Dunford, Andrew J.; Tai, Yu-Tzu; Chavda, Selina J.; Boehner, Cody; Neuse, Carl Jannes; Rahmat, Mahshid; Dutta, Ankit; Casneuf, Tineke; Verona, Raluca; Kastritis, Efstathis; Trippa, Lorenzo; Stewart, Chip; Walker, Brian A.; Davies, Faith E.; Dimopoulos, Meletios-Athanasios; Bergsagel, P. Leif; Yong, Kwee; Morgan, Gareth J.; Aguet, François; Getz, Gad; Ghobrial, Irene M.; Medicine, School of Medicine
    Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models.
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    Perspectives on the Risk-Stratified Treatment of Multiple Myeloma
    (American Association for Cancer Research, 2022) Davies, Faith E.; Pawlyn, Charlotte; Usmani, Saad Z.; San-Miguel, Jesus F.; Einsele, Hermann; Boyle, Eileen M.; Corre, Jill; Auclair, Daniel; Cho, Hearn Jay; Lonial, Sagar; Sonneveld, Pieter; Stewart, A. Keith; Bergsagel, P. Leif; Kaiser, Martin F.; Weisel, Katja; Keats, Jonathan J.; Mikhael, Joseph R.; Morgan, Kathryn E.; Ghobrial, Irene M.; Orlowski, Robert Z.; Landgren, C. Ola; Gay, Francesca; Caers, Joseph; Chng, Wee Joo; Chari, Ajai; Walker, Brian A.; Kumar, Shaji K.; Costa, Luciano J.; Anderson, Kenneth C.; Morgan, Gareth J.; Medicine, School of Medicine
    The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.