Identification of prognostic genes in the acute myeloid leukemia microenvironment

Shaoxin Huang,Qihan Zhao,Lei Yang,Wang Xin,Wenyan Fan,Biyu Zhang,Denggang Fu

doi:10.18632/aging.102477

Abstract

The tumor microenvironment (TME) has a strong influence on the progression, therapeutic response, and clinical outcome of acute myeloid leukemia (AML), one of the most common hematopoietic malignancies in adults. In this study, we identified TME-related genes associated with AML prognosis. Gene expression profiles from AML patients were downloaded from TCGA database, and immune and stromal scores were calculated using the ESTIMATE algorithm. Immune scores were correlated with clinical features such as FAB subtypes and patient’s age. After categorizing AML cases into high and low score groups, an association between several differentially expressed genes (DEGs) and overall survival was identified. Functional enrichment analysis of the DEGs showed that they were primarily enriched in the immune response, inflammatory response, and cytokine activity, and were involved in signaling processes related to hematopoietic cell lineage, B cell receptor, and chemokine pathways. Two significant modules, dominated respectively by CCR5 and ITGAM nodes, were identified from the PPI network, and 20 hub genes were extracted. A total of 112 DEGs correlated with poor overall survival of AML patients, and 11 of those genes were validated in a separate TARGET-AML cohort. By identifying TME-associated genes, our findings may lead to improved prognoses and therapies for AML.

Highlights

Acute myeloid leukemia (AML) is one of the most prevalent and aggressive blood cancers in adults, accounting for about 1% of all cancers [1,2,3]
No significant correlations between immune or stromal scores and patients’ gender or history of neoadjuvant treatment were observed using two-tailed Student’s t-tests, while immune scores showed a positive association with both cytogenetic risk category and age (Supplementary Figure 1)
These findings suggest that the analysis of immune and stromal scores may aid in the diagnosis and characterization of specific AML subtypes

Summary

Introduction

Acute myeloid leukemia (AML) is one of the most prevalent and aggressive blood cancers in adults, accounting for about 1% of all cancers [1,2,3]. AML is characterized by accumulation of immature myeloid hematopoietic cells, especially in the bone marrow. The main therapeutic strategy for AML, i.e. intensive induction chemotherapy and postremission therapy, has remained basically unchanged for the last 30 years, without substantial improvement in patient survival [6, 7]. Remarkable remissions can be initially attained through chemotherapy in most AML patients, complete disease elimination remains rare. Promising approaches have been proposed, such as chimeric antigen receptor (CAR) T-cell therapy targeting CD33 combined with allogeneic hematopoietic cell transplantation [8, 9]. 75% of patients are www.aging-us.com still at risk of disease relapse and succumb to the disease within 5 years from diagnosis [10]

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