
==== Front
bioRxiv
BIORXIV
bioRxiv
Cold Spring Harbor Laboratory

10.1101/2024.05.15.593193
preprint
1
Article
A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma
Pilcher William C.
Yao Lijun
Gonzalez-Kozlova Edgar
Pita-Juarez Yered
Karagkouni Dimitra
Acharya Chaitanya R.
Michaud Marina E
Hamilton Mark
Nanda Shivani
Song Yizhe
Sato Kazuhito
Wang Julia T.
Satpathy Sarthak
Ma Yuling
Schulman Jessica
D’Souza Darwin
Jayasinghe Reyka G.
Cheloni Giulia
Bakhtiari Mojtaba
Pabustan Nick
Nie Kai
Foltz Jennifer A.
Saldarriaga Isabella
Alaaeldin Rania
Lepisto Eva
Chen Rachel
Fiala Mark A.
Thomas Beena E
Cook April
Dos Santos Junia Vieira
Chiang I-ling
Figueiredo Igor
Fortier Julie
Slade Michael
Oh Stephen T.
Rettig Michael P.
Anderson Emilie
Li Ying
Dasari Surendra
Strausbauch Michael A
Simon Vernadette A
Immune Atlas Consortium
Rahman Adeeb H http://orcid.org/0000-0002-8620-3161

Chen Zhihong http://orcid.org/0000-0001-7403-7015

Lagana Alessandro
DiPersio John F.
Rosenblatt Jacalyn
Kim-Schulze Seunghee
Dhodapkar Madhav V
Lonial Sagar
Kumar Shaji
Bhasin Swati S http://orcid.org/0000-0001-5172-420X

Kourelis Taxiarchis
Vij Ravi
Avigan David
Cho Hearn J
Mulligan George
Ding Li
Gnjatic Sacha
Vlachos Ioannis S
Bhasin Manoj
17 5 2024
2024.05.15.593193http://biorxiv.org/lookup/doi/10.1101/2024.05.15.593193
nihpp-2024.05.15.593193.pdf
ABSTRACT

Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.
==== Body
pmc
