Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.

Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-lin...

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Autores principales:	Sarah Huet, Pascale Cony-Makhoul, Maël Heiblig, Isabelle Tigaud, Sophie Gazzo, Amine Belhabri, Denis Souche, Mauricette Michallet, Jean-Pierre Magaud, Sandrine Hayette, Franck Nicolini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/498ed52ee0b7482794675902f313cfd5
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spelling	oai:doaj.org-article:498ed52ee0b7482794675902f313cfd52021-11-25T06:01:14ZMajor molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.1932-620310.1371/journal.pone.0106250https://doaj.org/article/498ed52ee0b7482794675902f313cfd52014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0106250https://doaj.org/toc/1932-6203Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy. In this study, we evaluated the ability of the control gene GUS to identify relevant thresholds for known therapeutic decision levels (BCR-ABL1/ABL1IS = 10% and 0.1%). We then defined the most relevant cut-offs for early molecular response markers (transcript level at 3 months, halving time and log reduction between diagnosis and 3 months of treatment) using GUS or ABL1. We demonstrated that, although both control genes could be used (in an equivalent way) to accurately assess early molecular response, the BCR-ABL1/GUS level at diagnosis is impacted by the higher GUS copy number over-expressed in CML cells, thus negatively impacting its ability to completely replace ABL1 at diagnosis. Furthermore, we pointed out, for the first time, that it would be helpful to monitor BCR-ABL1 levels at an earlier time point than that currently performed, in order to assess response to first-line tyrosine-kinase inhibitors and consider a potential switch of therapy as early as possible. We evaluated this optimal time point as being 19 days after the start of treatment in our cohort.Sarah HuetPascale Cony-MakhoulMaël HeibligIsabelle TigaudSophie GazzoAmine BelhabriDenis SoucheMauricette MichalletJean-Pierre MagaudSandrine HayetteFranck NicoliniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e106250 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah Huet Pascale Cony-Makhoul Maël Heiblig Isabelle Tigaud Sophie Gazzo Amine Belhabri Denis Souche Mauricette Michallet Jean-Pierre Magaud Sandrine Hayette Franck Nicolini Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.
description	Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy. In this study, we evaluated the ability of the control gene GUS to identify relevant thresholds for known therapeutic decision levels (BCR-ABL1/ABL1IS = 10% and 0.1%). We then defined the most relevant cut-offs for early molecular response markers (transcript level at 3 months, halving time and log reduction between diagnosis and 3 months of treatment) using GUS or ABL1. We demonstrated that, although both control genes could be used (in an equivalent way) to accurately assess early molecular response, the BCR-ABL1/GUS level at diagnosis is impacted by the higher GUS copy number over-expressed in CML cells, thus negatively impacting its ability to completely replace ABL1 at diagnosis. Furthermore, we pointed out, for the first time, that it would be helpful to monitor BCR-ABL1 levels at an earlier time point than that currently performed, in order to assess response to first-line tyrosine-kinase inhibitors and consider a potential switch of therapy as early as possible. We evaluated this optimal time point as being 19 days after the start of treatment in our cohort.
format	article
author	Sarah Huet Pascale Cony-Makhoul Maël Heiblig Isabelle Tigaud Sophie Gazzo Amine Belhabri Denis Souche Mauricette Michallet Jean-Pierre Magaud Sandrine Hayette Franck Nicolini
author_facet	Sarah Huet Pascale Cony-Makhoul Maël Heiblig Isabelle Tigaud Sophie Gazzo Amine Belhabri Denis Souche Mauricette Michallet Jean-Pierre Magaud Sandrine Hayette Franck Nicolini
author_sort	Sarah Huet
title	Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.
title_short	Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.
title_full	Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.
title_fullStr	Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.
title_full_unstemmed	Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.
title_sort	major molecular response achievement in cml patients can be predicted by bcr-abl1/abl1 or bcr-abl1/gus ratio at an earlier time point of follow-up than currently recommended.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/498ed52ee0b7482794675902f313cfd5
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Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.

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