# Immuno and Epigenetics of Hematopoietic Cell Transplantation

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $387,519

## Abstract

HLA-matched and mismatched related and unrelated donor hematopoietic cell transplantation
can cure life-threatening blood disorders. The unmet needs of patients are to identify the optimal
transplant donor, and to lower risks of acute and chronic graft-versus-host disease (GVHD),
relapse and mortality. We recently discovered that the level of expression of HLA-C and HLA-
DP allotypes defines (non)permissive mismatches. Patient mismatching for high-expression
allotypes is associated with high risks of GVHD and mortality compared to low-expression
allotypes and should be avoided where possible. In HLA-A,B,C,DR,DQ,DP-matched unrelated
donor transplantation, possession of high-expression HLA-DP allotypes is associated with high
risk of GVHD compared to no high-expression allotypes. These data firmly demonstrate that the
amount of HLA protein is as important as the kind of HLA protein. We have convincing data that
HLA-DR and DQ expression is allotype-specific. We propose that HLA-matched and
mismatched related and unrelated transplantation can be improved with knowledge of HLA-DR
and DQ expression. The specific aims are to: determine HLA-DR and DQ allotype and
haplotype-specific expression; define the 5’, coding, 3’ and XL9 region variants for diverse DR-
DQ alleles; relate regulatory sequence variation to expression, and define the clinical
significance of DR/DQ expression in matched and mismatched transplantation. This proposal
will fill the knowledge gap in the HLA barrier as defined by expression. The information will
increase the safety, efficacy and availability of transplantation for patients in need of this life-
saving therapy.

## Key facts

- **NIH application ID:** 10216189
- **Project number:** 5R01CA218285-05
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Effie W Petersdorf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $387,519
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216189

## Citation

> US National Institutes of Health, RePORTER application 10216189, Immuno and Epigenetics of Hematopoietic Cell Transplantation (5R01CA218285-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216189. Licensed CC0.

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