Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets

被引：0

作者：

Rueda, Luz Yurany Moreno ^{[1
]}

Wang, Hua ^{[1
]}

Akagi, Keiko ^{[2
]}

Dang, Minghao ^{[1
]}

Vora, Amishi ^{[1
]}

Qin, Li ^{[1
]}

Lee, Hans C. ^{[1
]}

Patel, Krina K.

Lin, Pei ^{[3
]}

Mery, David E. ^{[4
]}

Zhan, Fenghuang ^{[4
]}

Shaughnessy Jr, John D. ^{[4
]}

Yi, Qing ^{[5
]}

Song, Yang ^{[1
]}

Jiang, Bo ^{[2
]}

Gillison, Maura L. ^{[2
]}

Thomas, Sheeba K. ^{[1
]}

Weber, Donna M. ^{[1
]}

Diao, Lixia ^{[6
]}

Wang, Jing ^{[6
]}

Kuiatse, Isere ^{[1
]}

Manasanch, Elisabet E. ^{[1
]}

Symer, David E. ^{[1
,7
]}

Orlowski, Robert Z. ^{[1
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Houston, TX USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX USA

[4] Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR USA

[5] Houston Methodist Dr Mary & Ron Neal Canc Ctr, Dept Canc Biol Med, Houston Methodist Dr, Houston, TX USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX USA

[7] VA Boston Healthcare Syst, Dept Med, Boston, MA USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

来源：

CELL REPORTS MEDICINE | 2025年 / 6卷 / 02期

关键词：

MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; QUALITY-CONTROL; MOUSE MODEL; CANCER; INHIBITOR; MAT2A; DISCOVERY; PROGNOSIS; APOPTOSIS;

D O I：

10.1016/j.xcrm.2024.101925

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models. Moreover, functional studies show a role of lysosomal-associated membrane protein family member-5 (LAMP5), which is uniquely expressed in neoplastic PCs, in tumor progression and aggressiveness via interactions with c-MYC. Finally, a monoclonal antibody recognizing cell-surface LAMP5 shows efficacy as an antibody-drug conjugate and in a chimeric antigen receptor-guided T-cell format. These studies provide additional insights into myeloma biology and identify potential targeted therapeutic approaches that can be applied to reverse myeloma progression.

引用

页数：27

共 75 条

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