EClinicalMed: A new genetic mutation site related to the outcome of hematopoietic stem cell transplantation in patients with hematological malignancies!

The identification of non-human leukocyte antigen (HLA) genetic risk factors may improve the survival rate of patients after allogeneic blood or bone marrow transplantation (BMT) through additional site matching or individualized risk prediction
.
Researchers speculate that non-HLA locus variation has a significant contribution to the 1-year overall survival (OS), disease-related mortality (DRM) or transplant-related mortality (TRM) after BMT derived from unrelated donors (URD) and carry out the relevant analyzes to verify the findings recently published in the lancet on child Journal

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Non-HLA locus variation has a significant contribution to the 1-year overall survival (OS), disease-related mortality (DRM) or transplant-related mortality (TRM) after BMT derived from a non-relative donor (URD) non-HLA locus Variants have a significant contribution to the 1-year overall survival (OS), disease-related mortality (DRM) or transplant-related mortality (TRM) after BMT derived from unrelated donors (URD).

This is a study of 2887 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL) from two independent cohorts (2000-2011 ) and their ≥8/8 Genome-wide Association Analysis ( GWAS ) performed in HLA-matched URD
.

2887 GWAS patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL)

Variants associated with overall survival

Variants associated with overall survival

Through the meta-analysis of the two cohorts, multiple non-HLA locus variants were found in the whole genome and are closely related to the clinical outcome of patients after transplantation: overall survival (OS) and the rs9990017 locus variation on the MBNL1 gene of the recipient and LINC02774 gene rs10927108 donor site - receptor gene Related mismatches (risk 1.
4, 95% CI 1.
24-1.
56 than [the HR], respectively, P = 3.
3 × 10 ^-8 and 1.
34, 95% CI 1.
21-1.
48 , p=2.
0×10 ^-8 )
.

Overall survival (OS) receptor MBNL1 on gene rs9990017 site variants and LINC02774 gene rs10927108 Receptor Gene Related mismatch - donor sites overall survival (OS) receptor MBNL1 on gene rs9990017 site variation and LINC02774 gene rs10927108 donor site - receptor gene Related mismatch of MBNL1 rs9990017 LINC02774 rs10927108 ^{-8 -8}

Variants associated with disease-related mortality

Variants associated with disease-related mortality

Disease-related mortality (DRM) and PCNX4 of the donor genome ( rs79076914 , HR 1.
7, 95% CI 1.
41–2.
05, p=3.
15×10 ^-8 ), LINC01194 ( rs79498125 , HR 1.
86, 95% CI 1.
49–2.
31, p =2.
84×10 ^-8 ), ARID5B( rs2167710 , HR 1.
5, 95% CI 1.
31--1.
73, p=6.
9×10 ^-9 ) and CT49 ( rs32250 , HR 1.
44, 95% CI 1.
26--1.
64, p=2.
6×10 ^-8 ) is related to the locus variation
.

Disease-related mortality (DRM) and the donor genome disease-related mortality (DRM) and the donor genome PCNX4 PCNX4 PCNX4 rs79076914 ^-8 LINC01194 LINC01194 LINC01194 rs79498125 ^-8 ARID5BARID5B ARID5B rs2167710 ^-9 CT49 CT49 CT49 rs32250 ^-8 on Locus variation is related
.
The locus variation on the related

.

Variants associated with transplant mortality

Transplant-related mortality (TRM) and the rs141591562 mutation of the TRM gene in the recipient genome (HR 2.

33, 95% CI 1.

Transplant-related mortality (TRM) and the recipient genome TRM gene rs141591562 site variants related mortality (TRM) and the graft recipient genome TRM gene rs141591562 site variants TRM rs141591562 ^-8 and EPGN and MTHF2DL between gene rs75868097 site for member - receptor genotype mismatches and EPGN and MTHF2DL between gene rs75868097 site donor - acceptor genotype mismatch EPGN MTHF2DL rs75868097 ^-9 Related Related

In conclusion, the results of this study prove for the first time that non-HLA common genetic variants of new gene loci with biochemical functions can also significantly affect the one-year survival rate after URD-BMT ; it provides new insights for donor selection and can guide treatment strategies And after future verification and functional research, two personalized risk predictions will be provided

The non-HLA common genetic variation of the new gene locus with biochemical function can also significantly affect the one-year survival rate after URD-BMT The non-HLA common genetic variation of the new gene locus with biochemical function can also significantly affect the post URD-BMT One-year survival rate

Original source:

Original source:

Theresa Hahn, et al.

Novel genetic variants associated with mortality after unrelated donor allogeneic hematopoietic cell transplantation in this message