Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults and is
characterized by transformed hematopoietic progenitor cells that fail to reach terminal
differentiation, are continuously proliferating, and overpopulate the bone marrow from where
they enter the blood system and circulate throughout the body. AML patients treated with
chemotherapy often achieve non-durable remission that results in relapse and higher mortality
rates. In culture, when HL-60 AML cells are treated with phorbol 12-myristate 13-acetate
(PMA), the cells undergo cell cycle arrest, differentiation into macrophage-like cells, and
eventually apoptosis. PMA is too toxic in patients to be used as a therapeutic, due to its effects
on normal cells, but the mechanisms of phenotypic change in HL-60 cells in response to PMA
can be elucidated and serve to identify possible therapeutic targets.
Sprouty homolog 2 (SPRY2) is one of the 1250 genes that change in expression during
the PMA response. SPRY2 belongs to the Sprouty family of proteins which are modulators of
the MAPK/ERK pathway. Inhibition of the constitutively activated ERK (Extracellular Signal-
Regulated Kinase) pathway in AML cell lines has been shown to cause a decrease in cell growth
and proliferation, and an increase in apoptosis. High levels of SPRY2 expression in patient
samples have been correlated with an improved prognosis in at least 10 different cancer types,
and AML patient data shows that patients with higher SPRY2 expression have slower disease
progression and better overall survival. In this study, it has been shown that SPRY2
overexpression can cause the downregulation of ERK signaling in HL-60 cells. Additionally,
SPRY2 may play a role in the induction of apoptosis in HL-60 cells.