SPRED1 Is Downregulated and a Prognostic Biomarker in Adult Acute Myeloid Leukemia

Rui Zhang1, Yan Zhang1, Xianglan Lu2

  • 1Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Frontiers in Oncology
|March 17, 2020
PubMed

Insights

Sprouty-Related EVH1 Domain-Containing Protein1 (SPRED1) is downregulated in acute myeloid leukemia (AML) and predicts treatment response. Lower SPRED1 levels indicate poorer survival in non-acute promyelocytic leukemia (non-APL) patients.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy.
  • Identifying reliable prognostic biomarkers is crucial for AML patient management.
  • The role of Sprouty-Related EVH1 Domain-Containing Protein1 (SPRED1) in AML pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the expression and prognostic significance of SPRED1 in adult AML.
  • To explore the functional role of SPRED1 in AML cell lines.
  • To evaluate SPRED1 as a potential therapeutic target.

Main Methods:

  • Quantitative mRNA expression analysis of SPRED1 in bone marrow samples from AML, ALL, and healthy controls.
  • Immunocytochemistry and ELISA for SPRED1 protein and serum levels.
  • Survival analysis correlating SPRED1 expression with clinical outcomes.
  • In vitro experiments overexpressing SPRED1 in AML cell lines (THP-1).

Main Results:

  • SPRED1 mRNA and protein levels were significantly downregulated in AML patients compared to controls and ALL patients.
  • Decreased SPRED1 expression correlated with specific AML subtypes (M2, M3) and poorer prognosis in non-APL.
  • SPRED1 expression increased upon achieving complete remission.
  • Overexpression of SPRED1 in vitro reduced ERK phosphorylation, induced apoptosis, and inhibited proliferation.

Conclusions:

  • SPRED1 is a downregulated biomarker in adult AML and a predictor of treatment response.
  • Reduced SPRED1 expression is an independent prognostic factor for non-APL patients.
  • Targeting the Ras-MAPK pathway, potentially through SPRED1 modulation, offers a promising therapeutic strategy for AML with SPRED1 downregulation.

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