Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

被引：194

作者：

Ledergor, Guy ^{[1
,2
]}

Weiner, Assaf ^{[1
]}

Zada, Mor ^{[1
]}

Wang, Shuang-Yin ^{[1
]}

Cohen, Yael C. ^{[3
,4
]}

Gatt, Moshe E. ^{[5
,6
]}

Snir, Nimrod ^{[4
,7
]}

Magen, Hila ^{[4
,8
]}

Koren-Michowitz, Maya ^{[4
,9
]}

Herzog-Tzarfati, Katrin ^{[4
,9
]}

Keren-Shaul, Hadas ^{[1
,10
]}

Bornstein, Chamutal ^{[1
]}

Rotkopf, Ron ^{[10
]}

Yofe, Ido ^{[1
]}

David, Eyal ^{[1
]}

Yellapantula, Venkata ^{[11
,12
]}

Kay, Sigalit ^{[3
]}

Salai, Moshe ^{[4
,7
]}

Ben Yehuda, Dina ^{[5
,6
]}

Nagler, Arnon ^{[4
]}

Shvidel, Lev ^{[6
,13
]}

Orr-Urtreger, Avi ^{[4
,14
]}

Halpern, Keren Bahar ^{[15
]}

Itzkovitz, Shalev ^{[15
]}

Landgren, Ola ^{[16
]}

San-Miguel, Jesus ^{[17
]}

Paiva, Bruno ^{[17
]}

Keats, Jonathan J. ^{[18
]}

Papaemmanuil, Elli ^{[12
]}

Avivi, Irit ^{[3
,4
]}

Barbash, Gabriel I. ^{[19
]}

Tanay, Amos ^{[20
,21
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[2] Tel Aviv Sourasky Med Ctr, Dept Internal Med, Tel Aviv, Israel

[3] Tel Aviv Sourasky Med Ctr, Dept Hematol, Tel Aviv, Israel

[4] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[5] Hadassah Med Ctr, Dept Hematol, Jerusalem, Israel

[6] Hebrew Univ Jerusalem, Fac Med, Jerusalem, Israel

[7] Tel Aviv Sourasky Med Ctr, Dept Orthoped, Tel Aviv, Israel

[8] Chaim Sheba Med Ctr, Hematol Div, Ramat Gan, Israel

[9] Assaf Harofeh Med Ctr, Dept Hematol, Zerifin, Israel

[10] Weizmann Inst Sci, Life Sci Core Facil, Rehovot, Israel

[11] Mem Sloan Kettering Canc Ctr, Ctr Hematol Malignancies, 1275 York Ave, New York, NY 10021 USA

[12] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[13] Kaplan Med Ctr, Hematol Inst, Rehovot, Israel

[14] Tel Aviv Sourasky Med Ctr, Genet Inst, Tel Aviv, Israel

[15] Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot, Israel

[16] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA

[17] Clin Univ Navarra, CIMA, CIBER ONC CB16 12 00369, Pamplona, Spain

[18] Translat Genom Res Inst, Integrated Canc Genom, Phoenix, AZ USA

[19] Weizmann Inst Sci, Bench Bedside Program, Rehovot, Israel

[20] Weizmann Inst Sci, Dept Comp Sci & Appl Math, Rehovot, Israel

[21] Weizmann Inst Sci, Dept Biol Regulat, Rehovot, Israel

来源：

NATURE MEDICINE | 2018年 / 24卷 / 12期

基金：

以色列科学基金会; 欧洲研究理事会;

关键词：

MULTIPLE-MYELOMA; RNA-SEQ; MUTATIONS; PROTEIN; PROGRESSION; EXPRESSION; GAMMOPATHY; DIAGNOSIS; BIOMARKER; MGUS;

D O I：

10.1038/s41591-018-0269-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.

引用

页码：1867 / +

页数：29

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