Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS

被引：162

作者：

Barreyro, Laura ^{[1
]}

Will, Britta ^{[1
]}

Bartholdy, Boris ^{[1
]}

Zhou, Li ^{[2
]}

Todorova, Tihomira I. ^{[1
]}

Stanley, Robert F. ^{[1
]}

Ben-Neriah, Susana ^{[3
,4
]}

Montagna, Cristina ^{[5
,6
,7
]}

Parekh, Samir ^{[1
,7
,8
]}

Pellagatti, Andrea ^{[9
]}

Boultwood, Jacqueline ^{[9
]}

Paietta, Elisabeth ^{[7
,8
]}

Ketterling, Rhett P. ^{[10
]}

Cripe, Larry ^{[11
]}

Fernandez, Hugo F. ^{[12
]}

Greenberg, Peter L. ^{[13
]}

Tallman, Martin S. ^{[14
]}

Steidl, Christian ^{[3
,4
]}

Mitsiades, Constantine S. ^{[15
,16
]}

Verma, Amit ^{[2
,7
,8
]}

Steidl, Ulrich ^{[1
,7
,8
]}

机构：

[1] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA

[2] Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA

[3] Univ British Columbia, Ctr Lymphoid Canc, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada

[4] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada

[5] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA

[6] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA

[7] Montefiore Med Ctr, Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA

[8] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med Oncol, Bronx, NY 10467 USA

[9] John Radcliffe Hosp, Leukaemia & Lymphoma Res Mol Haematol Unit, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England

[10] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA

[11] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA

[12] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[13] Stanford Univ, Ctr Canc, Hematol Div, Stanford, CA 94305 USA

[14] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA

[15] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[16] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

来源：

BLOOD | 2012年 / 120卷 / 06期

基金：

美国国家卫生研究院;

关键词：

ACUTE MYELOID-LEUKEMIA; WORLD-HEALTH-ORGANIZATION; EXPRESSION; GENE; INTERLEUKIN-1-BETA; KINASE; MARKER; CLASSIFICATION; PHENOTYPE; RASGRP3;

D O I：

10.1182/blood-2012-01-404699

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cellular and interpatient heterogeneity and the involvement of different stem and progenitor compartments in leukemogenesis are challenges for the identification of common pathways contributing to the initiation and maintenance of acute myeloid leukemia (AML). Here we used a strategy of parallel transcriptional analysis of phenotypic long-term hematopoietic stem cells (HSCs), short-term HSCs, and granulocyte-monocyte progenitors from individuals with high-risk (-7/7q-) AML and compared them with the corresponding cell populations from healthy controls. This analysis revealed dysregulated expression of 11 genes, including IL-1 receptor accessory protein (IL1RAP), in all leukemic stem and progenitor cell compartments. IL1RAP protein was found to be overexpressed on the surface of HSCs of AML patients, and marked cells with the -7/7q- anomaly. IL1RAP was also overexpressed on HSCs of patients with normal karyotype AML and high-risk myelodysplastic syndrome, suggesting a pervasive role in different disease subtypes. High IL1RAP expression was independently associated with poor overall survival in 3 independent cohorts of AML patients (P = 2.2 x 10(-7)). Knockdown of IL1RAP decreased clonogenicity and increased cell death of AML cells. Our study identified genes dysregulated in stem and progenitor cells in -7/7q- AML, and suggests that IL1RAP may be a promising therapeutic and prognostic target in AML and high-risk myelodysplastic syndrome. (Blood. 2012;120(6):1290-1298)

引用

页码：1290 / 1298

页数：9

共 52 条

[1] IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells [J].