4.6 Article

Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression

期刊

BLOOD ADVANCES
卷 6, 期 1, 页码 152-164

出版社

ELSEVIER
DOI: 10.1182/bloodadvances.2021004962

关键词

Progression of AML is associated with pro-inflammatory media-tors through altered expression levels of CR1; DPEP1; and ST18; Upregulated CD6 and downregulated INSR are nodes in gene expression networks linked to AML relapse; according to machine learning analysis

资金

  1. Swedish Research Council [2018-05973, sens2017604, sens2018512, 2013-03486]
  2. Knut and Alice Wallenberg Foundation [KAW 2013-0159]
  3. Swedish Childhood Cancer Foundation [PR2013-0070, TJ2013-0045]
  4. Swedish Cancer Society [CAN2013/489]
  5. Kjell and Marta Beijer Foundation
  6. Polish National Science Centre [DEC-2015/16/W/NZ2/00314]
  7. University of Washington, Seattle
  8. National Institute of Allergy and Infectious Diseases, Division of AIDS, National Institutes of Health [HHSN272201700010I]
  9. The eSSence program
  10. Vinnova [2013-03486] Funding Source: Vinnova
  11. Swedish Research Council [2013-03486] Funding Source: Swedish Research Council

向作者/读者索取更多资源

Numerous studies have been conducted to understand the genomic and transcriptomic lesions driving acute myeloid leukemia (AML) initiation. However, there is limited knowledge about the molecular characteristics of longitudinal AML samples and the challenges of relapse and therapy resistance. Our study identified differentially expressed genes associated with short event-free survival and AML relapse, providing insights into AML progression and potential personalized drug targets.
Numerous studies have been performed over the last decade to exploit the complexity of genomic and transcriptomic lesions driving the initiation of acute myeloid leukemia (AML). These studies have helped improve risk classification and treatment options. Detailed molecular characterization of longitudinal AML samples is sparse, however; meanwhile, relapse and therapy resistance represent the main challenges in AML care. To this end, we performed transcriptome-wide RNA sequencing of longitudinal diagnosis, relapse, and/or pri-mary resistant samples from 47 adult and 23 pediatric AML patients with known mutational background. Gene expression analysis revealed the association of short event-free survival with overexpression of GLI2 and IL1R1, as well as downregulation of ST18. Moreover, CR1 downregulation and DPEP1 upregulation were associated with AML relapse both in adults and children. Finally, machine learning-based and network-based analysis identified overex -pressed CD6 and downregulated INSR as highly copredictive genes depicting important relapse-associated characteristics among adult patients with AML. Our findings highlight the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments to improve cure rates in AML.

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