Phytosphingosine promotes megakaryocytic differentiation of myeloid leukemia cells

Abstract

We report that phytosphingosine, a sphingolipid found in many organisms and implicated in cellular signaling, promotes megakaryocytic differentiation of myeloid leukemia cells. Specifically, phytosphingosine induced several hallmark changes associated with megakaryopoiesis from K562 and HEL cells including cell cycle arrest, cell size increase and polyploidization. We also confirmed that cell type specific markers of megakaryocytes, CD41a and CD42b are induced by phytosphingosine. Phospholipids with highly similar structures were unable to induce similar changes, indicating that the activity of phytosphingosine is highly specific. Although phytosphingosine is known to activate p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis, the signaling mechanisms involved in megakaryopoiesis appear to be distinct. In sum, we present another model for dissecting molecular details of megakaryocytic differentiation which in large part remains obscure. [BMB Reports 2015; 48(12): 691-695]

Long Noncoding RNA (lncRNA) Small Nucleolar RNA Host Gene 5 (SNHG5) Regulates Proliferation, Differentiation, and Apoptosis of K562 Cells in Chronic Myeliod Leukemia

“…CD14 is the marker antigen of monocytes, and is mainly expressed in monocytes [26]. CD42b is the megakaryocyte differentiation antigen [10]. In the present study, the results showed that downregulation of SNHG5 significantly increased the expression of CD11b, CD14, and CD42b, indicating that K562 cells tended to differentiate into mature granulocytes, monocytes, and megakaryocyte.…”

“…The K562 cell line is a human myelogenous leukemia cell line from a highly undifferentiated progenitor of the megakaryocytic and erythrocytic lineages, with potential for erythroid and megakaryocyte differentiation, and it is currently the major cell model used for research of cellular differentation and screening of medical treatment for CML [8,9]. Differentiation-inducing therapy seems to be a promising strategy for CML [10,11], and the discover of a potential differentiation inducer or molecule has become an important focus of CML treatment.…”

2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate enhances thrombopoietin–induced megakaryocytic differentiation and plateletogenesis

“…Staining for F-actin with phalloidin to delineate cellular boundaries and counterstaining with 4′-6-Diamidino-2-phenylindole (DAPI) were carried out as previously described (11).…”

“…Generation and purification of large quantities of TPO suitable for application in cell culture-based production is likely to be highly costly. Here, we describe an alternate strategy utilizing ( R )-TEMOSPho, a synthetic chemical previously shown to induce megakaryocytic differentiation of myeloid leukemia cells, as a supplement to TPO (11, 12). Specifically, we show that ( R )-TEMOSPho, which cannot by itself induce efficient MK differentiation of murine HSCs, can enhance TPO activity in megakaryocytic differentiation and plateletogenesis.…”

Tetrandrine antagonizes acute megakaryoblastic leukaemia growth by forcing autophagy‐mediated differentiation

“…This gives researchers hope that they will eventually develop ways to force the AMKL cells to exit the proliferative cell cycle and undergo terminal differentiation (Wen et al ., ). A series of studies using agents that specifically promote the terminal differentiation of leukaemia cells into megakaryocytes are in development (Ojima et al ., ; Liu et al ., ; Han et al ., ). Of note, it has been demonstrated that autophagy is an important event for megakaryocytic differentiation of the human leukaemia cell line K562 (Colosetti et al ., ; Cao et al ., ), which has been extensively used as a model to study megakaryocyte differentiation.…”