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An integrated trans...
An integrated transcriptome analysis in T-cell acute lymphoblastic leukemia links DNA methylation subgroups to dysregulated TAL1 and ANTP homeobox gene expression
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- Haider, Zahra (author)
- Umeå universitet,Patologi
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- Larsson, Pär (author)
- Umeå universitet,Patologi
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- Landfors, Mattias, 1977- (author)
- Umeå universitet,Patologi
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- Köhn, Linda, 1979- (author)
- Umeå universitet,Onkologi,Patologi
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Schmiegelow, Kjeld (author)
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Flaegstad, Trond (author)
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Kanerva, Jukka (author)
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- Heyman, Mats (author)
- Karolinska Institutet
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- Hultdin, Magnus (author)
- Umeå universitet,Patologi
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- Degerman, Sofie, 1977- (author)
- Umeå universitet,Patologi
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(creator_code:org_t)
- 2018-12-21
- 2019
- English.
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In: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 8:1, s. 311-324
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Abstract
Subject headings
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- Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- BEX1
- DNA methylation
- HOXA
- pediatric acute lymphoblastic leukemia
- TAL1
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Haider, Zahra
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Larsson, Pär
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Landfors, Mattia ...
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Köhn, Linda, 197 ...
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Schmiegelow, Kje ...
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Flaegstad, Trond
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show more...
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Kanerva, Jukka
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Heyman, Mats
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Hultdin, Magnus
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Degerman, Sofie, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Pediatrics
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Cancer Medicine
- By the university
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Umeå University
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Karolinska Institutet