9-(2-Phosphonyl-methoxyethyl)-adenine promotes erythrocytic differentiation and disrupts cell replication in chronic myelogenous leukemia K562 cells

When hematopoietic stem cells undergo disruption of cellular differentiation during
hematopoiesis, it can result in the formation of cancer cells. Differentiation therapies are being
investigated as a new type of cancer treatment that involves the induction of cancer cells to undergo
cellular differentiation into homologues of normally functioning cells, such as erythrocytes, which can
then undergo cell death at an accelerated rate compared to cancer cells. In this particular study, the ability
of human chronic myelogenous leukemia (CML) K562 cells to undergo erythrocytic differentiation in
response to the inducing agent PMEA (9-(2-Phosphonyl-methoxy ethyl)-adenine) is investigated. PMEA
has been shown to both halt cell replication by stalling S-phase, and promote erythrocytic differentiation
in K562 cells. In order to further test the effectiveness of this inducer to promote erythrocytic
differentiation, the concentration of gamma-globin (a protein subunit of fetal hemoglobin) was measured
in both induced and uninduced K562 cell cultures via qRT-PCR and western blotting. The ability of
PMEA to halt cell cycle progression was also measured via a cell growth curve and the presence of
hemoglobin was measured via benzidine staining. The results indicate that those cells exposed to PMEA
underwent slowed cell replication and expressed hemoglobin, and subsequently gamma-globin, at a
higher concentration than those cells not exposed to PMEA. In summary, the findings reveal that PMEA
was able to promote the erythrocytic differentiation of K562 cells, and provide information that supports
differentiation therapies as a method for cancer treatment in the future.