Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan

Abstract Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with P...

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Autores principales:	Yin-Chen Hsu, Chih-Hsiang Yu, Yan-Ming Chen, Kathryn G. Roberts, Yu-Ling Ni, Kai-Hsin Lin, Shiann-Tarng Jou, Meng-Yao Lu, Shu-Huey Chen, Kang-Hsi Wu, Hsiu-Hao Chang, Dong-Tsamn Lin, Shu-Wha Lin, Ze-Shiang Lin, Wei-Tzu Chiu, Chia-Ching Chang, Bing-Ching Ho, Charles G. Mullighan, Sung-Liang Yu, Yung-Li Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f04befddc3f4e6aa76357fc7ad5066b
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spelling	oai:doaj.org-article:7f04befddc3f4e6aa76357fc7ad5066b2021-12-02T15:53:59ZPhiladelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan10.1038/s41598-021-85213-62045-2322https://doaj.org/article/7f04befddc3f4e6aa76357fc7ad5066b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85213-6https://doaj.org/toc/2045-2322Abstract Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.Yin-Chen HsuChih-Hsiang YuYan-Ming ChenKathryn G. RobertsYu-Ling NiKai-Hsin LinShiann-Tarng JouMeng-Yao LuShu-Huey ChenKang-Hsi WuHsiu-Hao ChangDong-Tsamn LinShu-Wha LinZe-Shiang LinWei-Tzu ChiuChia-Ching ChangBing-Ching HoCharles G. MullighanSung-Liang YuYung-Li YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yin-Chen Hsu Chih-Hsiang Yu Yan-Ming Chen Kathryn G. Roberts Yu-Ling Ni Kai-Hsin Lin Shiann-Tarng Jou Meng-Yao Lu Shu-Huey Chen Kang-Hsi Wu Hsiu-Hao Chang Dong-Tsamn Lin Shu-Wha Lin Ze-Shiang Lin Wei-Tzu Chiu Chia-Ching Chang Bing-Ching Ho Charles G. Mullighan Sung-Liang Yu Yung-Li Yang Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
description	Abstract Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.
format	article
author	Yin-Chen Hsu Chih-Hsiang Yu Yan-Ming Chen Kathryn G. Roberts Yu-Ling Ni Kai-Hsin Lin Shiann-Tarng Jou Meng-Yao Lu Shu-Huey Chen Kang-Hsi Wu Hsiu-Hao Chang Dong-Tsamn Lin Shu-Wha Lin Ze-Shiang Lin Wei-Tzu Chiu Chia-Ching Chang Bing-Ching Ho Charles G. Mullighan Sung-Liang Yu Yung-Li Yang
author_facet	Yin-Chen Hsu Chih-Hsiang Yu Yan-Ming Chen Kathryn G. Roberts Yu-Ling Ni Kai-Hsin Lin Shiann-Tarng Jou Meng-Yao Lu Shu-Huey Chen Kang-Hsi Wu Hsiu-Hao Chang Dong-Tsamn Lin Shu-Wha Lin Ze-Shiang Lin Wei-Tzu Chiu Chia-Ching Chang Bing-Ching Ho Charles G. Mullighan Sung-Liang Yu Yung-Li Yang
author_sort	Yin-Chen Hsu
title	Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
title_short	Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
title_full	Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
title_fullStr	Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
title_full_unstemmed	Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
title_sort	philadelphia chromosome-negative b-cell acute lymphoblastic leukaemia with kinase fusions in taiwan
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7f04befddc3f4e6aa76357fc7ad5066b
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Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan

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