title: Differential profile of PIP4K2A expression in hematological malignancies.
abstract: PIP4K2A is a lipid kinase that phosphorylates PtdIns5P, generating PtdIns4,5P2. 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.
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Keli
authors.initials: K
authors.lastname: Lima
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Daniela Maria
authors.initials: DM
authors.lastname: Ribeiro
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Paula de Melo
authors.initials: Pde M
authors.lastname: Campos
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Sara Teresinha Olalla
authors.initials: ST
authors.lastname: Saad
authors.affiliation: Department of Clinical Pathology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Sonati
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil. Electronic address: jamachadoneto@gmail.com.
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C514871:PIP4K2A protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor)
keywords: Alpha; Cell viability; Leukemia; Myelodysplastic syndromes; PIP4K2A; Phosphatidylinositol; Phosphatidylinositol-5-phosphate 4-kinase; Type II