ABSTRACT
Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified ('B-other') cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases. Limma analysis revealed an association between high expression of STAP1 and BCR signaling genes. However, STAP1 expression and pre-BCR signaling were not causally related: cytoplasmic Igµ levels were not abnormal in cases with high levels of STAP1 and stimulation of pre-BCR signaling did not induce STAP1 expression. To elucidate the role of STAP1 in BCP-ALL survival, expression was silenced in two human BCP-ALL cell lines. Knockdown of STAP1 did not reduce the proliferation rate or viability of these cells, suggesting that STAP1 is not a likely candidate for precision medicines. Moreover, high expression of STAP1 was not predictive for an unfavorable prognosis of BCR-ABL1-like and non-BCR-ABL1-like B-other cases. Remarkably, DUX4-rearrangements and intragenic ERG deletions, were enriched in cases harboring high expression of STAP1.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Homeodomain Proteins/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chromosome Aberrations , Fusion Proteins, bcr-abl/genetics , Humans , Polymorphism, Single Nucleotide , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , RNA Interference , RNA, Small Interfering/metabolism , Receptors, Antigen, B-Cell/metabolism , Signal Transduction , Transcriptional Regulator ERG/genetics , Transcriptional Regulator ERG/metabolismABSTRACT
Worldwide, oocyte donors donate voluntarily or receive varying amounts of money for donation. This raises ethical questions regarding the appropriateness of financial compensation, and the possibility of undue inducement and exploitation of oocyte donors. Are these donors capable of making an independent, well-considered decision? Regarding this matter, it is important to examine aspects such as autonomy-connectedness and self-esteem. In this cross-sectional study, demographic characteristics and donation motivations were assessed in 92 women who attended the University Medical Center (UMC) Utrecht as potential oocyte donors between June 2012 and July 2016. Demographic characteristics were assessed. Motivations were recorded in semi-structured interviews (response rate 59%). The Rosenberg Self-Esteem Scale was used to assess level of self-esteem. The Autonomy-Connectedness Scale was used to measure the level of autonomy-connectedness. The typical oocyte donor at the UMC Utrecht is a well-educated, employed, 31-year-old woman living with her partner in a completed family with two children, and donating on altruistic grounds. The donors showed higher autonomy-connectedness scores than the average female Dutch population and do not lack self-esteem (questionnaire response rate 66%). Concerns regarding exploitation and attraction of women with lower socioeconomic status, with shortcomings in autonomy-connectedness and self-esteem, could not be confirmed in this group.
