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A new mutant NPM1/I...
A new mutant NPM1/IDH2R140- and PML-RARA-associated lncRNA MALNC plays a role in AML biology, prognosis and drug response
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- Neddermeyer, Anne (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Sören Lehmann
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- Björklund, My (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Sören Lehmann
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- Dimitris, Kanellis (författare)
- Department of Biochemistry and Biophysics, Solna, Karolinska Institute,Jiri Bartek
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- Struyf, Nona (författare)
- Department of Oncology-Pathology, Karolinska Institute, Solna, Sweden,Päivi Östling
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- Karlsson, Kasper (författare)
- Department of Oncology-Pathology, Karolinska Institute, Solna, Sweden,Olli-Pekka Kallioniemi
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- Qu, Ying (författare)
- Department of Medicine, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
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- Mareschal, Sylvain (författare)
- LYSARC, The Lymphoma Academic Research Organization, Lyon, France
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- Cozzi, Elisabetta (författare)
- Department of Medicine, Karolinska Institute, Solna, Sweden,Sören Lehmann
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- Zhong, Xiangfu (författare)
- Department of Medicine, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
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- Bengtzén, Sofia (författare)
- Department of Medicine, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
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- Nilsson, Christer (författare)
- Department of Medicine, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
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- Erkers, Tom (författare)
- Department of Oncology-Pathology, Karolinska Institute, Solna, Sweden,Olli-Pekka Kallioniemi
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- Kallioniemi, Olli-Pekka (författare)
- Department of Oncology-Pathology, Karolinska Institute, Solna, Sweden,Olli-Pekka Kallioniemi
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- Lennartsson, Andreas (författare)
- Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden,Andreas Lennartsson
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- Lehmann, Sören (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden,Sören Lehmann
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by poor prognosis that requires better understanding of its disease biology and new tools for suitable risk stratification and effective treatments. Long non-coding RNAs (lncRNAs) are involved in numerous molecular mechanisms, are implicated in tumor biology and can serve as clinical biomarkers, yet their role remains mostly unclear in AML. In this study, the aim was to discover and characterize lncRNAs implicated in AML and to describe their role in AML biology. Further aims were to explore their use as prognostic or predictive biomarkers. Using whole-transcriptome analysis, a novel lncRNA, here named MALNC, was identified. MALNC had elevated expression in two large AML cohorts compared to normal CD34+ cells. Clinical correlation analyses indicated that MALNC was almost uniquely expressed in patients with PML-RARA fusion gene and with co-mutated isocitrate dehydrogenase-2 R140 and nucleophosmin-1 (IDH2R140/NPM1). MALNC expression was specifically high at the promyelocytic stage and decreased with maturation in leukemic and normal cells. High MALNC expression associated independently with better overall survival. CRISPR-Cas9-knockout in promyelocytic cell lines impaired proliferation, colony formation and all-trans retinoic acid (ATRA)-induced differentiation. Also, MALNC-knockout dramatically sensitized cells to arsenic trioxide (ATO), ATO-ATRA combinatorial and Bcl-2-inhibitor venetoclax treatment as well as associated with cyclin-dependent kinase (Cdk)-inhibitor resistance. In conclusion, MALNC is overexpressed in certain subgroups of AML and could play a role during normal and leukemic hematopoietic maturation. Furthermore, it correlates with response to anti-leukemic drugs, which suggests a role as a predictive marker to drug response and survival in AML.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- acute myeloid leukemia (AML)
- long non-coding RNAs (lncRNAs)
- RNA-sequencing
- CRISPR-Cas9
- all-trans retinoic acid (ATRA)
- arsenic trioxide (ATO)
- venetoclax
- drug response
- prognosis
- Molekylär medicin
- Molecular Medicine
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)
- Av författaren/redakt...
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Neddermeyer, Ann ...
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Björklund, My
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Dimitris, Kanell ...
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Struyf, Nona
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Karlsson, Kasper
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Qu, Ying
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visa fler...
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Mareschal, Sylva ...
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Cozzi, Elisabett ...
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Zhong, Xiangfu
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Bengtzén, Sofia
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Nilsson, Christe ...
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Erkers, Tom
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Kallioniemi, Oll ...
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Lennartsson, And ...
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Lehmann, Sören
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Hematologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Av lärosätet
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Uppsala universitet