SNPs in suppressor of fused (SUFU) associated with acute GVHD (SJ-14-0018)

St. Jude Reference #SJ-14-0018

Description

Many factors, related to both the donor and the recipient, have been identified as potential risk factors for the development of graft versus host disease (GVHD). The most important risk factor is the genetic disparity between the donor and recipient in human leukocyte antigen (HLA).  Relatively little is known about non-HLA genetic factors in the recipient that may contribute to the development of GVHD. Researchers at St. Jude performed a genome-wide analysis of germline single nucleotide polymorphisms (SNPs) in patients with a history of acute lymphoblastic or myeloid leukemia (ALL, AML) who underwent hematopoietic stem cell transplant (HSCT), investigating the association between recipient SNPs and the development of acute GVHD.  The researchers then identified two SNPs in suppressor of fused (SUFU) that were associated with acute GVHD. 

Researchers at St. Jude have identified a SNP in the SUFU gene was found to be associated with the incidence of acute GVHD in pediatric and young adult patients who underwent allogeneic HSCT. Researchers discovered transplant recipients who were homozygous for the major SUFU allele (CC) were more susceptible to acute GVHD than recipients who were heterozygous, so the researchers developed a novel and simple assay for SUFU allele typing that is expedient for testing patients undergoing HSCT and has the potential to be a useful diagnostic aiding with GVHD clinical management. There is no existing technology for SUFU allele typing.

These results also suggest that the SNP is a molecular marker for GVHD risk and SUFU is a potential therapeutic target for GVHD prevention, so this may be useful in drug discovery and development.

In 2010, about 20,000 bone marrow transplants (BMTs) were performed in the US.  Approximately 12,000 were autologous and approximately 8,000 were allogeneic.  Worldwide, there were about 60,000 BMTs overall, about 34,000 autologous and 26,000 allogeneic/ The number of patients over the age of 50 has been steadily increasing over the last decade and based on the latest available data grew from 8% in 2000 to 21% in 2005 and 27% in 2007.


 

Keywords

Graft versus host disease (GVHD), human leukocyte antigen (HLA), single nucleotide polymorphisms (SNPs), acute lymphoblastic or myeloid leukemia (ALL, AML), hematopoietic stem cell transplant (HSCT), suppressor of fused (SUFU), diagnostic, allele typing, therapeutic target


 

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