Aleynick, Nathan
Mayo Clinic
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Citations 2
Genetic risk and immune dysregulation of classic Hodgkin lymphoma transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma: a multicentric study
Yan, Mingfei , Parikh, S., Melo, Michelly K. Sampaio de, Hampel, P., Aleynick, Nathaniel, Chan, A. O., Eren, Özgür Can , Lopez, Katherine, Cohen, Alexa, Roshal, Mikhail , Lim, Megan S., Zhang, Yanming, Jaffe, Elaine S., King, Rebecca L., Parikh, Sameer A. , Aleynick, Nathan , Parikh, Sameer A , Sampaio De Melo, Michelly K , Hampel, Paul J , Aleynick, Nathan , Chan, Alexander , Lim, Megan S , Boiocchi, Leonardo , Dogan, Ahmet , Sinha, Sutapa , Chaffee, Kari G. , Kay, Neil E , Xiao, Wenbin , Hampel, Paul J. , Doǧan, Ahmet , Zhang, Yanming , Sinha, Sutapa , Rabe, Kari G. , Kay, Neil E. , Jaffe, Elaine S. , King, Rebecca L.
No container title available | May 21, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
ABSTRACT Richter transformation of Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into classic Hodgkin lymphoma (CHL-RT) is rare and remains incompletely understood. Two histologic subtypes are recognized: type 1 (CLL/SLL with scattered Hodgkin/Reed-Sternberg (HRS) cells) and type 2 (HRS cells within a polymorphous inflammatory background). In this multi-institutional study of 77 patients with CHL-RT (27 type 1 and 50 type 2), we characterized immune evasion markers, PD-L1 / PD-L2 copy number alterations, tumor microenvironment, and performed targeted next-generation sequencing on 37 CLL/SLL samples. HRS cells in CHL-RT displayed immune-evasion phenotypes similar to de novo CHL, though PD-L1 expression was lower in type 1 cases. PD-L1/PD-L2 gain/polysomy were frequent (83.3%). CLL/SLL with CHL-RT harbored increased mutations in XPO1, FBXW7, BIRC3, TRAF3 , and HLA-A versus reference CLL/SLL. Similar mutational profiles, demographics, and survival outcomes support a biological continuum between type 1 and type 2 CHL-RT, with distinct genetic features in CLL/SLL predisposing to CHL transformation. STATEMENT OF SIGNIFICANCE Classic Hodgkin lymphoma-type Richter transformation arises from convergent Hodgkin-like immune evasion on a genetically primed CLL/SLL background. Through integrated genomic and tumor microenvironment analyses in a large multicenter cohort, we establish this as a biologically coherent entity and provide rationale for PD-L1/PD-L2-directed therapeutic strategies.
A High-Fiber, Plant-Based Diet in Myeloma Precursor Disorders: Results from the NUTRIVENTION Clinical Trial and Preclinical Vk*MYC Model
Shah, Urvi A. , Cogrossi, Laura Lucia , Garcés, Juan‐José , Policastro, Anna , Castro, Francesca , Derkach, Andriy , Fei, Teng , DeWolf, Susan , Grioni, Matteo , Sisti, Sofia , Blaslov, Jenna , Adintori, Peter , McAvoy, Devin , Baichoo, Mirae , Paredes, Jenny , Anuraj, Aishwarya , Pohl, Charlotte , Zinsmeyer, Victoria , Gipson, Brianna , Marchigiani, Camilla , Pagani, Sara , Salehi, Erica , Block, Torin , Korde, Neha , Tan, Carlyn , Hultcrantz, Malin , Hassoun, Hani , Scordo, Michael , Lahoud, Oscar , Landau, Heather , Peled, Jonathan U. , Chesi, Marta , Mailankody, Sham , D’Souza, Anita , Iyengar, Neil M. , Adintori, Peter A , Hosszu, Kinga K , McAvoy, Devin , Baichoo, Mirae , Cross, Justin R , Paredes, Jenny , Anuraj, Aishwarya , Raj, Sandeep S , Pohl, Charlotte , Zordan, Paola , Zinsmeyer, Victoria , Jesus Faustino Ramos, Ruben J , Lorenzoni, Marco , Gipson, Brianna , Maclachlan, Kylee , Gradissimo, Ana , Boiocchi, Leonardo , Aleynick, Nathan , Marchigiani, Camilla , Pagani, Sara , Salehi, Erica , Koche, Richard P , Chaligne, Ronan , Block, Torin , Korde, Neha , Tan, Carlyn R , Hultcrantz, Malin , Hassoun, Hani , Shah, Gunjan L , Scordo, Michael , Lahoud, Oscar B , Chung, David J , Landau, Heather , Peled, Jonathan U , Clementi, Nicola , Chesi, Marta , Bergsagel, P. Leif , Mailankody, Sham , Pollak, Michael N , D'Souza, Anita , Landgren, C Ola , Chimonas, Susan , Giralt, Sergio , Usmani, Saad , Iyengar, Neil M , Lesokhin, Alexander M , van den Brink, Marcel R M , Bellone, Matteo , Shah, Urvi A , Derkach, Andriy , Garces, Juan-Jose , Fei, Teng , Maclachlan, Kylee , Aleynick, Nathan , Shah, Gunjan L. , Bergsagel, P. Leif , Pollak, Michaël , Landgren, Ola , Giralt, Sergio , Usmani, Saad Z. , Lesokhin, Alexander M. , Bellone, Matteo
Cancer Discovery | December 4, 2025 | Volume: 16 | Issue: 4 | Pages: 697-720
Abstract Consumption of a Western diet and high body mass index (BMI) are risk factors for progression from premalignant phenotypes to multiple myeloma, a hematologic cancer. In the NUTRIVENTION trial (NCT04920084), we administered a high-fiber, plant-based diet (HFPBD; meals for 12 weeks, coaching for 24 weeks) to 23 participants with myeloma precursor states and elevated BMI. The intervention was feasible and improved quality of life and modifiable risk factors: metabolic (BMI, insulin resistance), microbiome (diversity, composition), and immune (inflammation, monocyte subsets). Disease progression trajectory improved (n = 2) or was stable. Findings were translated to Vk*MYC mice modeling the myeloma precursor state, in which a high-fiber diet (HFD) delayed disease progression through improved metabolism and microbiome composition, leading to increased short-chain fatty acid production that reinvigorated antitumor immunity and inhibited tumor growth. These effects from fiber consumption were independent of calorie restriction and weight loss. A HFD is a low-risk intervention that may delay progression to myeloma. Significance: A HFPBD in participants with precursor plasma cell disorders and an elevated BMI improved metabolic, microbiome, and immune biomarkers of disease. In a subset, it may delay progression to myeloma. In mouse models, a HFD delayed progression to myeloma independent of calorie restriction. See related commentary by Fairfield and Reagan, p. 623