1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma

Published in Nature Communications. Here is a link to the article.

Regenstrief Institute authors: Kun Huang, PhD

This study uses single-cell multi-omic profiling of over 325,000 cells from 49 multiple myeloma patients to investigate disease progression and treatment resistance. Researchers identified a plasma cell subtype—relapsed/refractory plasma cells (RRPCs)—linked to poor outcomes, marked by chromosome 1q alterations, TP53 mutations, and elevated PHF19 expression. Findings suggest PHF19 may drive disease progression by regulating cell cycle inhibitors, possibly through the transcription factor PBX1, highlighting a potential target for therapeutic intervention.

Authors

Travis S. Johnson^1,2,3,4, Parvathi Sudha⁵, Enze Liu⁵, Nathan Becker⁵, Sylvia Robertson², Patrick Blaney⁶, Gareth Morgan⁶, Vivek S Chopra⁷, Cedric Dos Santos⁷, Michael Nixon⁸, Kun Huang^1,3,4, Attaya Suvannasankha^5,9, Mohammad Abu Zaid⁵, Rafat Abonour⁵, Brian A Walker^10,11

Affiliations

¹Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN, USA.

²Indiana Biosciences Research Institute, Indianapolis, IN, USA.

³Melvin and Bren Simon Comprehensive Cancer Center, Experimental and Developmental Therapeutics, School of Medicine, Indiana University, Indianapolis, IN, USA.

⁴Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, IN, USA.

⁵Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology and Oncology, School of Medicine, Indiana University, Indianapolis, IN, USA.

⁶Perlmutter Cancer Center, Langone Health, New York University, New York, NY, USA.

⁷Genentech Inc., South San Francisco, CA, USA.

⁸Roche Inc., Indianapolis, IN, USA.

⁹Roudebush VAMC, Indianapolis, IN, USA.

¹⁰Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, IN, USA. bw75@iu.edu.

¹¹Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology and Oncology, School of Medicine, Indiana University, Indianapolis, IN, USA. bw75@iu.edu.