PBX1: a key character of the hallmarks of cancer.

Pre-B-cell leukemia homeobox transcription factor 1 (PBX1) was first identified as part of a fusion protein resulting from the chromosomal translocation t(1;19) in pre-B cell acute lymphoblastic leukemias. Since then, PBX1 has been associated with important developmental programs, and its expression dysregulation has been related to multifactorial disorders, including cancer. As PBX1 overexpression in many cancers is correlated to poor prognosis, we sought to understand how this transcription factor contributes to carcinogenesis, and to organize PBX1's roles in the hallmarks of cancer. There is enough evidence to associate PBX1 with at least five hallmarks: sustaining proliferative signaling, activating invasion and metastasis, inducing angiogenesis, resisting cell death, and deregulating cellular energetics. The lack of studies investigating a possible role for PBX1 on the remaining hallmarks made it impossible to defend or refute its contribution on them. However, the functions of some of the PBX1's transcription targets indicate a potential engagement of PBX1 in the avoidance of immune destruction and in the tumor-promoting inflammation hallmarks. Interestingly, PBX1 might be a player in tumor suppression by activating the transcription of some DNA damage response genes. This is the first review organizing PBX1 roles into the hallmarks of cancer. Thus, we encourage future studies to uncover the PBX1's underlying mechanisms to promote carcinogenesis, for it is a promising diagnostic and prognostic biomarker, as well as a potential target in cancer treatment.

Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families.

The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome-Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0-fold (P = 0.036). Pre-B-cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3-fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild-type homozygote genotype had overexpression of PBX1. There is a 3-fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.

Gene variations in PBX1, LMX1A and SLITRK1 are associated with obsessive-compulsive disorder and its clinical features.

Genetic factors probably influence OCD development and a current hypothesis proposes that genes involved in the development of the central nervous system (CNS) are related to OCD. The aim of this study was to analyze six Single Nucleotide Polymorphisms (SNPs) in five genes with functions related to neurodevelopment in OCD. A total of 203 patient and 203 control samples were genotyped using the TaqMan® methodology. Statistically significant associations between OCD and PBX1 (rs2275558) in total sample (P = 0.002) and in males (P = 0.0003) were observed. Concerning symptom dimensions, the expression of neutralization showed a statistical significant association with LMX1A (rs4657411, P = 0.004) in total sample. We also observed significant association between LMX1A (rs4657411) and washing dimension in females (P = 0.01). Additionally, SLITRK1 (rs9593835) was significantly associated with checking dimension in male patients (P = 0.04). Our results indicate an important influence of neurodevelopment genes in the OCD susceptibility. Additional studies with larger samples are needed to confirm these results.

Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols.

Historically, t(1;19)(q23;p13.3) has been related to pre-B acute lymphoblastic leukemia (ALL) and associated with a poor prognosis. Current treatments have overcome this dismal outcome, but advantages in survival for the unbalanced group have been reported. We compared the outcome of balanced and unbalanced der(19)t(1;19) cases and also patients with t(1;19)/TCF3-PBX1 versus patients without this translocation, to assess its prognostic value. From January 1990 to December 2010, t(1;19)(q23;p13)/TCF3-PBX1 was detected in 48 cases. Patients were treated with Berlin-Frankfurt-Münster (BFM)-based protocols and classified into balanced (n = 17) and unbalanced (n = 23) groups. The probability of event-free survival (pEFS) (standard error) of patients with t(1;19)/TCF3-PBX1 was 85% (6%), for the unbalanced group 78% (10%), and 88% (8%) for the balanced. The pEFS of patients with t(1;19)/TCF3-PBX1 was significantly superior to that of patients without t(1;19)/TCF3-PBX1 (p-value <0.0001). Patients with t(1;19)/TCF3-PBX1 presented a good outcome with no differences between balanced and unbalanced subgroups. Thus, risk-adjustment therapy would not be necessary for cases with t(1;19)/TCF3-PBX1.