PIP4K2A and PIP4K2C transcript levels are associated with cytogenetic risk and survival outcomes in acute myeloid leukemia

Author(s)

Lima, Keli ^[1] ; Coelho-Silva, Juan Luiz ^{[2, 3]} ; Kinker, Gabriela Sarti ^[4] ; Pereira-Martins, Diego Antonio ^{[2, 3]} ; Traina, Fabiola ^[3] ; Carlos Magno Fernandes, Pedro Augusto ^[4] ; Markus, Regina Pekelmann ^[4] ; Lucena-Araujo, Antonio Roberto ^[2] ; Machado-Neto, Joao Agostinho ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Fed Pernambuco, Dept Genet, Recife, PE - Brazil

^[3] Med Sch Ribeirao Preto, Dept Internal Med, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Inst Biosci, Dept Physiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: CANCER GENETICS; v. 233, p. 56-66, APR 2019.
• Web of Science Citations: 0

Abstract

Phosphoinositide signaling pathway orchestrates primordial molecular and cellular functions in both healthy and pathologic conditions. Phosphatidylinositol-5-phosphate 4-kinase type 2 lipid kinase (PIP4K2) family, which compromises PIP4K2A, PIP4K2B and PIP4K2C, has drawn the attention in human cancers. Particularly in hematological malignancies, PIP4K2A was already described as an essential protein for a malignant phenotype, although the clinical and biological impact of PIP4K2B and PIP4K2C proteins have not being explored in the same extent. In the present study, we investigated the impact on clinical outcomes and gene network of PIP4K2A, PIP4K2B and PIP4K2C mRNA transcripts in acute myeloid leukemia (AML) patients included in The Cancer Genome Atlas (2013) study. Our results indicate that PIP4K2A and PIP4K2C, but not PIP4K2B, mRNA levels were significantly reduced in AML patients assigned to the favorable risk group (p < 0.05) and low levels of PIP4K2A and PIP4K2C positively affect clinical outcomes of AML patients (p < 0.05). Gene set enrichment analyses indicate that the expression of PIP4K2 genes is associated with biological process such as signal transduction, metabolism of RNA and genomic instability related-gene sets. In summary, our study provides additional evidence of the involvement of members of the PIP4K2 family, in particular PIP4K2A and PIP4K2C, in AML. (AU)

• FAPESP's process: 17/24993-0 - Investigation of Stathmin 1 and microtubule instability in phenotype of hematological neoplasms
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants