title: Analysis of the expression of PHTF1 and related genes in acute lymphoblastic leukemia.
abstract: BACKGROUND
  Previous study showed that downregulated BCL11B expression in T cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4 inhibited cell proliferation and induce apoptosis, which may be related to PHTF1 gene overexpression. The objective of this study was to investigate the expression of PHTF1 and related genes in ALL and further explore its function in T-ALL cell lines.
  
  
  METHODS
  Real-time PCR was used to determine the gene expression level of PHTF1 in hematologic malignancies. The PHTF1, BCL11B, FEM1B and Apaf-1 gene expression levels and correlations were analyzed in patients with primary ALL (including T-ALL and B-ALL) and healthy individuals (HIs). Inhibition and overexpression of PHTF1 by lentiviral transduction were performed using the Molt-4 and Jurkat cell lines. Cell growth and apoptosis were measured by the Cell Counting Kit-8 assay and flow cytometry, respectively. Upon PHTF1 overexpression, the BCL11B, FEM1B and Apaf-1 gene expression levels were determined by real-time PCR.
  
  
  RESULTS
  PHTF1 overexpression was found in both T-ALL (p = 0.004) and B-ALL (p < 0.001) groups compared with HIs group. A trend toward a negative correlation between the PHTF1 and BCL11B genes was detected for the T-ALL group, while positively correlated expression was found for the PHTF1 and BCL11B genes in HIs (P = 0.001). FEM1b and Apaf-1 overexpression was found in recently diagnosed ALL patients compared with HIs (p < 0.05). Positively correlated expression was found for the PHTF1, FEM1b and Apaf-1 genes in patients with ALL (p < 0.05) and HIs (p < 0.05). Direct up-regulation of PHTF1 expression inhibited the proliferation of Jurkat and Molt-4 cells and effectively induced apoptosis in Molt-4 cells. Direct inhibition of PHTF1 expression had no significant effect on the proliferation or apoptosis of Jurkat and Molt-4 cells. FEM1b and Apaf-1 overexpression, which did not obviously alter the BCL11B expression level, was detected in PHTF1-transduced T-ALL cell lines.
  
  
  CONCLUSIONS
  PHTF1 overexpression is responsible for regulating cell proliferation and apoptosis in T-ALL cell lines. PHTF1 may be a tumor-suppressor like gene and a therapeutic target for triggering the PHTF1-FEM1b-Apaf-1 apoptosis pathway.
authors.affiliation: Southern Medical University, 510515 Guangzhou, People's Republic of China ; Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Zesheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Lingji
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Minming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Deng
authors.affiliation: Institute of Hematology, Medical College, Jinan University, 510632 Guangzhou, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Hematology, Medical College, Jinan University, 510632 Guangzhou, People's Republic of China ; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, 510632 Guangzhou, People's Republic of China.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
keywords: ALL; Apaf-1; Apoptosis; BCL11B; FEM1b; Overexpression; PHTF1; Proliferation