Active enhancer and chromatin accessibility landscapes chart the regulatory network of primary multiple myeloma

Yi Jin, Kenian Chen, Ayla De Paepe, Eva Hellqvist, Aleksandra D. Krstic, Lauren Metang, Charlotte Gustafsson, Richard E. Davis, Yair M. Levy, Rakesh Surapaneni, Ann Wallblom, Hareth Nahi, Robert Mansson and Yin C. Lin

Key points

  • Gene regulatory features in multiple myeloma patients reveal a key regulatory network and epigenetic changes that underpin the disease.


Multiple myeloma (MM) is an aggressive cancer that originates from antibody-secreting plasma cells. While genetically and transcriptionally well characterized, the aberrant gene regulatory networks that underpin this disease remain poorly understood. Here, we mapped regulatory elements, open chromatin and transcription factor footprints in primary MM cells. In comparison to normal antibody-secreting cells, MM cells displayed consistent changes in enhancer activity that are connected to super-enhancer (SE)-mediated deregulation of transcription factor (TF) genes. MM cells also displayed widespread decompaction of heterochromatin that was associated with activation of regulatory elements and in a major subset of patients deregulation of the cAMP pathway. Finally, building SE-associated TF-based regulatory networks allowed identification of several novel TFs that are central to MM biology. Taken together, these findings significantly add to our understanding of the aberrant gene regulatory network that underpins MM.

  • Submitted September 25, 2017.
  • Accepted February 26, 2018.