Understanding transplant relapse of the myelodysplastic syndromes through early detection of residual disease among hematopoietic stem cells
Active Project Grant Awarded Last action
- Award ID
- F30HL178281
- Recipient
-
The University Of Texas Southwestern Medical Center UEI YZJ6DKPM4W63
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $303,545
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 50% complete
- Place of performance
- Dallas, TX 75390, USA
Award details come from USAspending.gov.
Description
- Abstract
- The myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow failure syndromes diagnosed in 15,000 patients annually within the united states and collectively carrying a 5-year survival rate of 35%. Hematopoietic stem cells (hscs) have been identified as the cell of origin for MDS, however their rarity has largely precluded their meaningful study, especially following treatment where hypocellular bone marrow samples yield exceedingly few cells to study. Therefore, little is known about their response to treatments, especially after allogeneic stem cell transplant (allosct). In preliminary studies, we have validated a new low- input targeted sequencing workflow using a panel of more than 250 blood cancer associated genes that can detect mutations in as few as 20 sorted cells. The long-term goal of this project is to elucidate the mechanisms necessary for cure of MDS by comparing the response of MDS hscs to allosct in patients who relapse VS. Who are cured. The specific aims are as follows: (1) to assess the potential for the detection of MDS hscs to predict for relapse, and (2) to elucidate the molecular and clonal evolution that MDS hscs undergo to persist following allosct. Specific aim 1 will apply a novel low-input sequencing protocol we have developed to patient samples following allosct to evaluate the variant frequencies of clinically identified MDS driver mutations in hscs and determine whether their detection correlates with relapse. Specific aim 2 will use mitochondrial lineage tracing in single-cell DNA- and RNA-sequencing studies to evaluate how both the transcriptional programs and sub- clonal composition of MDS hscs may evolve during allosct to promote relapse.
Transactions
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| Amendment | $42,959 | |
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| Original award | $42,959 |
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Quick answers
Who received award F30HL178281?
F30HL178281 was awarded to The University Of Texas Southwestern Medical Center by National Heart Lung and Blood Institute (National Institutes of Health) on July 23, 2025.
How much is award F30HL178281 worth?
$303,545 has been obligated on F30HL178281.
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