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CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms

Discrimination of Philadelphia‐negative myeloproliferative neoplasms (Ph‐MPNs) from reactive hypercytosis and myelofibrosis requires a constellation of testing including driver mutation analysis and bone marrow biopsies. We searched for a biomarker that can more easily distinguish Ph‐MPNs from react...

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Autores principales: Morishita, Soji, Yasuda, Hajime, Yamawaki, Saya, Kawaji, Hideya, Itoh, Masayoshi, Edahiro, Yoko, Imai, Misa, Kogo, Yasushi, Tsuneda, Satoshi, Ohsaka, Akimichi, Hayashizaki, Yoshihide, Ito, Masafumi, Araki, Marito, Komatsu, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893984/
https://www.ncbi.nlm.nih.gov/pubmed/33280191
http://dx.doi.org/10.1111/cas.14763
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author Morishita, Soji
Yasuda, Hajime
Yamawaki, Saya
Kawaji, Hideya
Itoh, Masayoshi
Edahiro, Yoko
Imai, Misa
Kogo, Yasushi
Tsuneda, Satoshi
Ohsaka, Akimichi
Hayashizaki, Yoshihide
Ito, Masafumi
Araki, Marito
Komatsu, Norio
author_facet Morishita, Soji
Yasuda, Hajime
Yamawaki, Saya
Kawaji, Hideya
Itoh, Masayoshi
Edahiro, Yoko
Imai, Misa
Kogo, Yasushi
Tsuneda, Satoshi
Ohsaka, Akimichi
Hayashizaki, Yoshihide
Ito, Masafumi
Araki, Marito
Komatsu, Norio
author_sort Morishita, Soji
collection PubMed
description Discrimination of Philadelphia‐negative myeloproliferative neoplasms (Ph‐MPNs) from reactive hypercytosis and myelofibrosis requires a constellation of testing including driver mutation analysis and bone marrow biopsies. We searched for a biomarker that can more easily distinguish Ph‐MPNs from reactive hypercytosis and myelofibrosis by using RNA‐seq analysis utilizing platelet‐rich plasma (PRP)‐derived RNAs from patients with essential thrombocythemia (ET) and reactive thrombocytosis, and CREB3L1 was found to have an extremely high impact in discriminating the two disorders. To validate and further explore the result, expression levels of CREB3L1 in PRP were quantified by reverse‐transcription quantitative PCR and compared among patients with ET, other Ph‐MPNs, chronic myeloid leukemia (CML), and reactive hypercytosis and myelofibrosis. A CREB3L1 expression cutoff value determined based on PRP of 18 healthy volunteers accurately discriminated 150 driver mutation–positive Ph‐MPNs from other entities (71 reactive hypercytosis and myelofibrosis, 6 CML, and 18 healthy volunteers) and showed both sensitivity and specificity of 1.0000. Importantly, CREB3L1 expression levels were significantly higher in ET compared with reactive thrombocytosis (P < .0001), and polycythemia vera compared with reactive erythrocytosis (P < .0001). Pathology‐affirmed triple‐negative ET (TN‐ET) patients were divided into a high– and low–CREB3L1‐expression group, and some patients in the low‐expression group achieved a spontaneous remission during the clinical course. In conclusion, CREB3L1 analysis has the potential to single‐handedly discriminate driver mutation–positive Ph‐MPNs from reactive hypercytosis and myelofibrosis, and also may identify a subgroup within TN‐ET showing distinct clinical features including spontaneous remission.
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spelling pubmed-78939842021-03-02 CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms Morishita, Soji Yasuda, Hajime Yamawaki, Saya Kawaji, Hideya Itoh, Masayoshi Edahiro, Yoko Imai, Misa Kogo, Yasushi Tsuneda, Satoshi Ohsaka, Akimichi Hayashizaki, Yoshihide Ito, Masafumi Araki, Marito Komatsu, Norio Cancer Sci Original Articles Discrimination of Philadelphia‐negative myeloproliferative neoplasms (Ph‐MPNs) from reactive hypercytosis and myelofibrosis requires a constellation of testing including driver mutation analysis and bone marrow biopsies. We searched for a biomarker that can more easily distinguish Ph‐MPNs from reactive hypercytosis and myelofibrosis by using RNA‐seq analysis utilizing platelet‐rich plasma (PRP)‐derived RNAs from patients with essential thrombocythemia (ET) and reactive thrombocytosis, and CREB3L1 was found to have an extremely high impact in discriminating the two disorders. To validate and further explore the result, expression levels of CREB3L1 in PRP were quantified by reverse‐transcription quantitative PCR and compared among patients with ET, other Ph‐MPNs, chronic myeloid leukemia (CML), and reactive hypercytosis and myelofibrosis. A CREB3L1 expression cutoff value determined based on PRP of 18 healthy volunteers accurately discriminated 150 driver mutation–positive Ph‐MPNs from other entities (71 reactive hypercytosis and myelofibrosis, 6 CML, and 18 healthy volunteers) and showed both sensitivity and specificity of 1.0000. Importantly, CREB3L1 expression levels were significantly higher in ET compared with reactive thrombocytosis (P < .0001), and polycythemia vera compared with reactive erythrocytosis (P < .0001). Pathology‐affirmed triple‐negative ET (TN‐ET) patients were divided into a high– and low–CREB3L1‐expression group, and some patients in the low‐expression group achieved a spontaneous remission during the clinical course. In conclusion, CREB3L1 analysis has the potential to single‐handedly discriminate driver mutation–positive Ph‐MPNs from reactive hypercytosis and myelofibrosis, and also may identify a subgroup within TN‐ET showing distinct clinical features including spontaneous remission. John Wiley and Sons Inc. 2020-12-21 2021-02 /pmc/articles/PMC7893984/ /pubmed/33280191 http://dx.doi.org/10.1111/cas.14763 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Morishita, Soji
Yasuda, Hajime
Yamawaki, Saya
Kawaji, Hideya
Itoh, Masayoshi
Edahiro, Yoko
Imai, Misa
Kogo, Yasushi
Tsuneda, Satoshi
Ohsaka, Akimichi
Hayashizaki, Yoshihide
Ito, Masafumi
Araki, Marito
Komatsu, Norio
CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms
title CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms
title_full CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms
title_fullStr CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms
title_full_unstemmed CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms
title_short CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome–negative myeloproliferative neoplasms
title_sort creb3l1 overexpression as a potential diagnostic marker of philadelphia chromosome–negative myeloproliferative neoplasms
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893984/
https://www.ncbi.nlm.nih.gov/pubmed/33280191
http://dx.doi.org/10.1111/cas.14763
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