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Published on: October 11, 2018
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.
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.
Abstract:
We report herein that Sprouty-Related EVH1 Domain-Containing Protein1 (SPRED1) is downregulated and a prognostic biomarker in adult acute myeloid leukemia (AML). We determined mRNA levels of SPRED1 in the bone marrow mononuclear cells from adult patients, including 113 AMLs and 22 acute lymphoblastic leukemias (ALLs), as well as in 37 healthy control subjects. Significantly decreased SPRED1 mRNA expression was found in AML patients comparing to those in ALL patients and healthy controls, which was confirmed by immunocytochemistry analysis of SPRED1 protein and ELISA measurement of serum SPRED1 level. Further analysis demonstrated that SPRED1 expression was significantly higher for most patients at complete remission after induction treatment than at diagnosis. Moreover, SPRED1 expression was significantly downregulated in M2 and M3 types. Non-acute promyelocytic leukemia (non-APL) patients with decreased SPRED1 had significantly lower 2-year progression-free survival and event-free survival rates. In vitro, ectopic overexpression of SPRED1 leads to a decrease of extracellular signal-regulated kinase (ERK) phosphorylation, induction of apoptosis and reduction of proliferation of THP-1 cells. Our findings suggest SPRED1 is not only a predictor of treatment response, but also an independent prognostic factor for non-APL, and targeting Ras- Mitogen-activated protein kinase (MAPK) signaling may be a promising strategy for the treatment of AML with downregulation of SPRED1.
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