Differential profile of PIP4K2A expression in hematological malignancies

作者：Lima Keli; Ribeiro Daniela Maria; Campos Paula de Melo; Costa Fernando Ferreira; Traina Fabiola; Olalla Saad Sara Teresinha; Sonati Maria de Fatima; Machado Neto Joao Agostinho^*

来源：Blood Cells, Molecules, and Diseases, 2015, 55(3): 228-235.

DOI：10.1016/j.bcmd.2015.06.014

• Phosphatidylinositol-5-phosphate 4-kinase
• Type II
• Alpha
• PIP4K2A
• Leukemia
• Myelodysplastic syndromes
• Phosphatidylinositol
• Cell viability

PIP4K2A is a lipid kinase that phosphorylates PtdIns5P, generating PtdIns4,5P(2). Recently, PIP4K2A was identified as a potential target in acute myeloid leukemia cells. The objective of the present study was to investigate the PIP4K2A expression in hematological malignancies and verify the effects of PIP4K2A silencing on proliferation and survival of leukemia cell lines. PIP4K2A was found to be a cytoplasmic and nuclear protein with reduced levels in leukemia cell lines compared to normal leukocytes. PIP4K2A mRNA levels were significantly reduced in bone marrow cells from acute lymphoid leukemia (ALL) patients compared with healthy donors and in myelodysplastic syndromes (MDS) with >= 5% compared with <5% bone marrow blasts. Low PIP4K2A expression (lowest tertile versus 2 higher tertiles) negatively impacted overall survival of MDS patients by univariate analysis. PIP4K2A silencing did not modulate cell proliferation, clonogenicity and apoptosis of HEL and Namalwa leukemia cells. In summary, we characterized the expression of PIP4K2A in a cohort of patients with hematological malignancies and we found that PIP4K2A mRNA expression is downregulated in RAEB-1/RAEB-2 MDS and ALL cells, and PIP4K2A silencing does not modulate cell survival in HEL and Namalwa leukemia cells.

• 出版日期2015-10