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.

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.