AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

被引：108

作者：

Battula, V. Lokesh ^{[1
,2
]}

Le, Phuong M. ^{[1
]}

Sun, Jeffrey C. ^{[1
]}

Nguyen, Khoa ^{[1
]}

Yuan, Bin ^{[1
]}

Zhou, Ximin ^{[1
]}

Sonnylal, Sonali ^{[1
]}

McQueen, Teresa ^{[1
]}

Ruvolo, Vivian ^{[1
]}

Michel, Keith A. ^{[3
]}

Ling, Xiaoyang ^{[1
]}

Jacamo, Rodrigo ^{[1
]}

Shpall, Elizabeth ^{[4
]}

Wang, Zhiqiang ^{[5
]}

Rao, Arvind ^{[6
]}

Al-Atrash, Gheath ^{[4
]}

Konopleva, Marina ^{[1
]}

Davis, R. Eric ^{[5
]}

Harrington, Melvyn A. ^{[7
]}

Cahill, Catherine W. ^{[7
]}

Bueso-Ramos, Carlos ^{[8
]}

Andreeff, Michael ^{[1
,4
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Mol Hematol & Therapy, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Small Anim Imaging Facil, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

[7] Baylor Coll Med, Orthoped Surg, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd,Unit 425, Houston, TX 77030 USA

来源：

JCI INSIGHT | 2017年 / 2卷 / 13期

基金：

美国国家卫生研究院;

关键词：

BONE MORPHOGENETIC PROTEINS; IN-VIVO; FACTOR CTGF; STEM-CELLS; EXPRESSION; MARROW; BMP; PROGRESSION; RECEPTOR; NICHES;

D O I：

10.1172/jci.insight.90036

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, in particular in osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter the BM microenvironment to create a hospitable niche. Here, we report that acute myeloid leukemia (AML) cells, but not normal CD34(+) or CD33(+) cells, induce osteogenic differentiation in mesenchymal stromal cells (MSCs). In addition, AML cells inhibited adipogenic differentiation of MSCs. Mechanistic studies identified that AML-derived BMPs activate Smad1/5 signaling to induce osteogenic differentiation in MSCs. Gene expression array analysis revealed that AML cells induce connective tissue growth factor (CTGF) expression in BM-MSCs irrespective of AML type. Overexpression of CTGF in a transgenic mouse model greatly enhanced leukemia engraftment in vivo. Together, our data suggest that AML cells induce a preosteoblast-rich niche in the BM that in turn enhances AML expansion.

引用

页数：18

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