Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity

被引：804

作者：

van Galen, Peter ^{[1
,2
,3
,4
,5
]}

Hovestadt, Volker ^{[1
,2
,3
,4
,5
]}

Wadsworth, Marc H., II ^{[4
,6
,7
,8
]}

Hughes, Travis K. ^{[4
,6
,7
,8
]}

Griffin, Gabriel K. ^{[1
,2
,3
,4
,5
,9
]}

Battaglia, Sofia ^{[1
,2
,3
,4
,5
]}

Verga, Julia A. ^{[1
,2
,3
,4
,5
]}

Stephansky, Jason ^{[3
,9
,10
]}

Pastika, Timothy J. ^{[3
,9
,10
]}

Story, Jennifer Lombardi ^{[2
,5
]}

Pinkus, Geraldine S. ^{[9
]}

Pozdnyakova, Olga ^{[9
]}

Galinsky, Ilene ^{[10
]}

Stone, Richard M. ^{[10
]}

Graubert, Timothy A. ^{[2
,5
]}

Shalek, Alex K. ^{[4
,6
,7
,8
]}

Aster, Jon C. ^{[3
,9
]}

Lane, Andrew A. ^{[3
,10
]}

Bernstein, Bradley E. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02114 USA

[3] Harvard Med Sch, Ludwig Ctr, Boston, MA 02115 USA

[4] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[5] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[6] MIT, Dept Chem, Inst Med Engn & Sci, Cambridge, MA 02139 USA

[7] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[8] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[9] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[10] Dana Farber Canc Inst, Boston, MA 02215 USA

来源：

CELL | 2019年 / 176卷 / 06期

关键词：

STEM-CELLS; SUPPRESSOR-CELLS; LEUKEMIA; PROGENITOR; CANCER; GENOMICS; FUTURE;

D O I：

10.1016/j.cell.2019.01.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies.

引用

页码：1265 / +

页数：41

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