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Overexpression of amyloid precursor protein in acute myeloid leukemia enhances extramedullary infiltration by MMP-2
Ling Jiang1, Guopan Yu, Wei Meng
1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
It is known that leukemia patients with extramedullary infiltration (EMI) have a worse prognosis than patients without it. Recent data indicate that the amyloid precursor protein (APP) is involved in cell adhesion, motility, and proliferation. The expression of APP and its prognostic significance in acute myeloid leukemia (AML) have not been studied. Our study shows that AML/ETO(+) leukemia patients that overexpress APP easily get EMI and that their long-term survival rate is lower than patients without overexpression of APP. In an in vitro study, we knocked down APP in Kasumi-1 cells using small interfering RNA (siRNA). Transwell data show that siRNA/APP substantially impairs cell migration, but it does not inhibit cell proliferation. Furthermore, by quantitative real-time polymerase chain reaction and Western blot, we found that siRNA/APP decreases MMP-2 expression in vitro. Our study provides a novel clue that APP is involved in the extramedullary infiltration of leukemia by MMP-2.
Insights
Amyloid precursor protein (APP) overexpression in acute myeloid leukemia (AML) correlates with extramedullary infiltration and poorer survival. Reducing APP inhibits leukemia cell migration and MMP-2 expression, suggesting a role in disease spread.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Extramedullary infiltration (EMI) in leukemia patients is linked to a worse prognosis.
- Amyloid precursor protein (APP) is implicated in cell adhesion, motility, and proliferation.
- The prognostic role of APP in acute myeloid leukemia (AML) remains uninvestigated.
Purpose of the Study:
- To investigate the expression and prognostic significance of APP in AML.
- To explore the role of APP in the extramedullary infiltration of leukemia.
- To elucidate the mechanism by which APP influences leukemia cell behavior.
Main Methods:
- Analysis of APP expression in AML/ETO(+) leukemia patients.
- In vitro knockdown of APP using small interfering RNA (siRNA) in Kasumi-1 cells.
- Assessment of cell migration and proliferation using Transwell assays.
- Quantitative real-time polymerase chain reaction and Western blot to evaluate MMP-2 expression.
Main Results:
- AML/ETO(+) patients overexpressing APP showed a higher incidence of EMI and reduced long-term survival.
- siRNA-mediated knockdown of APP significantly impaired leukemia cell migration but not proliferation in vitro.
- APP knockdown led to decreased expression of MMP-2 in Kasumi-1 cells.
Conclusions:
- APP overexpression is a negative prognostic factor in AML, associated with increased extramedullary infiltration.
- APP plays a crucial role in regulating leukemia cell migration.
- APP may mediate extramedullary infiltration in leukemia through the MMP-2 pathway.
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