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| Status |
Public on Jun 15, 2022 |
| Title |
Cell free DNA 5-hydroxymethylcytosine as an emerging marker of acute myeloid leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Aberrant changes in 5-hydroxymethylcytosine (5hmC) are a unique epigenetic feature in many cancers including acute myeloid leukemia (AML). However, genome-wide analysis of 5hmC in plasma cell-free DNA (cfDNA) remains unexploited in AML patients. We used a highly sensitive and robust nano-5hmC-Seal technology and profiled genome-wide 5hmC distribution in 239 plasma cfDNA samples from 103 AML patients and 81 non-cancer controls. We developed a 5hmC diagnostic model that precisely differentiates AML patients from controls with high sensitivity and specificity. We also developed a 5hmC prognostic model that accurately predicts prognosis in AML patients. High weighted prognostic scores (wp-scores) in AML patients were significantly associated with adverse overall survival (OS) in both training (P = 3.31e-05) and validation (P = .000464) sets. The wp-score was also significantly associated with genetic risk stratification and displayed dynamic changes with varied disease burden. Moreover, we found that high wp-scores in a single gene, BMS1 and GEMIN5 predicted OS in AML patients in both the training set (P =.023 and .031, respectively) and validation set (P = 9.66e-05 and 0.011, respectively). Lastly, our study demonstrated the genome-wide landscape of DNA hydroxymethylation in AML and revealed critical genes and pathways related to AML diagnosis and prognosis. Our data reveal plasma cfDNA 5hmC signatures as sensitive and accurate markers for AML diagnosis and prognosis. Plasma cfDNA 5hmC analysis will be an effective and minimally invasive tool for AML management.
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| Overall design |
Examination of the 5-hydroxymethyl cytosine (5hmC) profiles from cell-free DNA from Acute myeloid leukemia patients in comparison to non-cancer controls
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| Contributor(s) |
Shao J, Li Z |
| Citation(s) |
35859008 |
| |
| Submission date |
Dec 24, 2020 |
| Last update date |
Aug 03, 2022 |
| Contact name |
Zejuan Li |
| E-mail(s) |
[email protected]
|
| Phone |
3462385129
|
| Organization name |
Houston Methodist Hospital
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| Department |
Department of Pathology and Genomic Medicine
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| Street address |
6565 Fannin St, MC227
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| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
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| Samples (164)
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| Relations |
| BioProject |
PRJNA687749 |
| SRA |
SRP299294 |
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