Last update 01 Nov 2024

VPREB1

Last update 01 Nov 2024

Basic Info

Synonyms

CD179 antigen-like family member A, CD179A, Immunoglobulin iota chain

+ [6]

Introduction

Associates with the Ig-mu chain to form a molecular complex that is expressed on the surface of pre-B-cells. This complex presumably regulates Ig gene rearrangements in the early steps of B-cell differentiation.

Drugs associated with VPREB1

VpreB1 ADC(Specifica)

Target

VPREB1

Mechanism

VPREB1 antagonists

Active Org.

Specifica, Inc.Startup

Originator Org.

Specifica, Inc.Startup

Active Indication

Acute Lymphoblastic Leukemia [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with VPREB1

100 Translational Medicine associated with VPREB1

0 Patents (Medical) associated with VPREB1

177

Literatures (Medical) associated with VPREB1

31 Dec 2024·Hematology

Construction of a five-gene-based prognostic model for relapsed/refractory acute lymphoblastic leukemia

Article

Author: Li, Ying ; Zhou, Bi ; Fang, Jing ; Wu, De ; Min, BoJie ; Chen, Qin ; Huang, Jin ; Zhu, Feng ; Liu, WenYuan

BACKGROUNDRelapsed/refractory acute lymphoblastic leukemia (R/R ALL) continues to be a major cause of mortality in children worldwide, with around 15% of ALL patients experiencing relapse and approximately 10% eventually dying from the disease. Early identification of R/R ALL in children has posed a longstanding clinical challenge.METHODGenetic analysis of survival outcomes in pediatric patients with ALL from the TARGET-ALL dataset revealed five risk score factors identified through the intersection of differential genes (relapse/non-relapse) from the GSE17703 and GSE6092 databases. A risk score equation was formulated using these factors and validated against prognostic data from 46 ALL cases at our institution. Patients from multiple datasets were stratified into high and low-score groups based on this equation. Protein-protein interaction networks (PPI) were then constructed using the intersecting differential genes from all three datasets to identify hub nodes and predict interacting transcription factors. Additionally, genes related to cell pyroptosis with varying expression across these datasets were screened, and a multifactorial ROC curve (incorporating risk score and differential expression of pyroptosis-related genes) was generated. Furthermore, relationships among variables in the predictive model were depicted using a nomogram, and model efficacy was assessed through decision curve analysis (DCA).RESULTSBy analyzing the TARGET-ALL, GSE17703, and GSE6092 databases, we developed a prognostic risk assessment model for pediatric ALL incorporating BAG2, EPHA4, FBXO9, SNX10, and WNK1. Validation of this model was conducted using data from 46 pediatric ALL cases obtained from our institution. Following the identification of 27 differentially expressed genes, we constructed a PPI and identified the top 10 hub genes (PTPRC, BTK, LCK, PRKCQ, CD3D, CD27, CD3G, BLNK, RASGRP1, VPREB1). Using this network, we predicted the top 5 transcription factors (HOXB4, MYC, SOX2, E2F1, NANOG). ROC and DCA were conducted on pyroptosis-related genes exhibiting differential expression and risk scores. Subsequently, a nomogram was generated, demonstrating the effectiveness of the risk score in predicting prognosis for pediatric ALL patients.CONCLUSIONSWe have developed a risk prediction model for pediatric R/R ALL utilizing the genes BAG2, EPHA4, FBXO9, SNX10, and WNK1. This model provides a scientific foundation for early identification of R/R ALL in children.

01 Dec 2024·Translational Oncology

Characterisation of cells markers associated with IKZF1plus in BCP-ALL

Article

Author: Lopes, Bruno A ; Maciel, Ana Luiza Tardem ; Figueiredo, Ariadne da Rocha ; Blunck, Caroline Barbieri ; Poubel, Caroline Pires ; Schramm, Márcia Trindade ; da Costa, Elaine Sobral ; Barbosa, Thayana C ; Land, Marcelo G.P. ; Land, Marcelo G P ; Lopes, Bruno A. ; Barbosa, Thayana C. ; Lins, Mecneide Mendes ; Gomes, Renan Garcia ; Mansur, Marcela Braga ; Aguiar, Thais Ferraz ; Ikoma-Coltutato, Maura Rosane Valério ; Emerenciano, Mariana

The presence of IKZF1 deletions has been associated with an increased relapse rate in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). There is a particular subset of IKZF1^del cases called IKZF1^plus (defined by the co-occurrence of IKZF1^del and deletions in CDKN2A/B, PAX5, or the PAR1 region, in the absence of ERG deletions), which is also associated with worse prognosis, but some recent studies have not found major differences between the IKZF1^del and IKZF1^plus groups. Therefore, the IKZF1^plus group still needs further comprehension and our study aims to characterise the molecular heterogeneity and identify molecular markers exclusively associated with IKZF1^plus. Two independent series of cases (TARGET, n = 125 and GenLAb, n = 60) were evaluated by segregating patients into 3 groups: IKZF1^plus, IKZF1^del, and IKZF1^wild. Differential expression analyses showed that the membrane protein-coding genes most associated with the IKZF1^plus group were: KCNA5, GREB1, EPOR, SDK1, and PTPRB. Notably, KCNA5 and GREB1 differential expression levels were validated in the GenLAb validation series. Regarding copy number alterations, we observed a high frequency of VPREB1 deletions in the IKZF1^plus group, as well as additional exclusive deletions in the CD200 and BTLA genes. Recent research suggests that the importance of the IKZF1^plus profile varies depending on the genetic subgroup. In this scenario, we found associations between IKZF1^plus and certain genes in BCP-ALL, being KCNA5 and GREB1 the most promising biomarkers for predicting IKZF1^plus. A deeper understanding of these genetic profiles will allow a better risk assessment and offer precise rationale for therapeutic strategies in BCP-ALL.

01 Aug 2024·Life Science Alliance

A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing

Article

Author: Arvidsson, Gustav ; Bunikis, Ignas ; Gezelius, Henrik ; Lysenkova Wiklander, Mariya ; Nordlund, Jessica ; Raine, Amanda ; Feuk, Lars ; Marincevic-Zuniga, Yanara ; Lundmark, Anders ; Ameur, Adam ; Bremer, Anna

The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21)ETV6::RUNX1translocation, is known to have a complex karyotype defined by a series of large-scale chromosomal rearrangements. Taken from a 15-yr-old at relapse, the cell line offers a practical model for the study of pediatric B-ALL. In recent years, short- and long-read DNA and RNA sequencing have emerged as a complement to karyotyping techniques in the resolution of structural variants in an oncological context. Here, we explore the integration of long-read PacBio and Oxford Nanopore whole-genome sequencing, IsoSeq RNA sequencing, and short-read Illumina sequencing to create a detailed genomic and transcriptomic characterization of the REH cell line. Whole-genome sequencing clarified the molecular traits of disrupted ALL-associated genes includingCDKN2A,PAX5,BTG1,VPREB1, andTBL1XR1, as well as the glucocorticoid receptorNR3C1. Meanwhile, transcriptome sequencing identified seven fusion genes within the genomic breakpoints. Together, our extensive whole-genome investigation makes high-quality open-source data available to the leukemia genomics community.

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