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Series GSE138702 Query DataSets for GSE138702
Status Public on Feb 03, 2020
Title Highly multiplexed proteomic assessment of the human bone marrow microenvironment reveals elevated levels of CCL23 in acute myeloid leukemia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Acute myeloid leukemia (AML) is a genetically heterogeneous disease that is characterized by abnormal clonal proliferation of myeloid progenitor cells found predominately within the bone marrow (BM) and blood. Recent studies suggest that genetic and phenotypic alterations in the BM microenvironment support leukemogenesis and allow leukemic cells to survive and evade chemotherapy-induced death. However, despite substantial evidence indicating the role of tumor-host interactions in AML pathogenesis, little is known about the complex microenvironment of the BM. To address this, we performed novel proteomic profiling of the non-cellular compartment of the BM microenvironment in AML patients (n=10) and age- and sex-matched healthy controls (n=10) using an aptamer-based, highly multiplexed, affinity proteomics platform (SOMAscan). We demonstrate that proteomic assessment of blood or RNA-sequencing of BM are suboptimal alternate screening strategies to determine the true proteomic composition of the extracellular compartment of the AML marrow microenvironment. Proteomic analysis showed 168 proteins significantly differed in abundance, with 91 proteins up-regulated and 77 proteins down-regulated in leukemic BM. A highly connected signaling network of cytokines and chemokines, including IL-8, was found to be the most prominent proteomic signature associated with AML in the BM microenvironment. We report the first description of significantly elevated levels of the myelosuppressive chemokine CCL23 (MPIF–1) in both AML and MDS patients and perform functional experiments supportive of a role in the suppression of normal hematopoiesis. This unique paired RNA-sequencing and proteomics dataset provides innovative mechanistic insights into AML and healthy aging and should serve as a useful public resource.
Overall design Total RNA sequencing of rRNA-depleted RNA was performed using the Illumina TruSeq Stranded Total RNA kit. Sequencing was performed on RNA isolated from bone marrow PAXgene tubes of 10 acute myeloid leukemia patients and 10 age- and sex-matched healthy donor controls.
Contributor(s) Gui G, Hourigan CS
Citation(s) 31985806
Submission date Oct 10, 2019
Last update date Jul 20, 2020
Contact name Christopher Hourigan
Phone 3014510257
Organization name National Heart Lung and Blood Institute, NIH
Department Hematology Branch
Lab Myeloid Malignancies
Street address Room 10CRC 5-5130, 10 Center Drive
City Bethesda
State/province Maryland
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (19)
GSM4116446 AML_1_S1
GSM4116447 AML_2_S5
GSM4116448 AML_3_S7
BioProject PRJNA576867
SRA SRP225068

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE138702_count.csv.gz 1.2 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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