Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We...

Full description

Bibliographic Details
Main Authors:	Vaclava Polivkova, Peter Rohon, Hana Klamova, Olga Cerna, Martina Divoka, Nikola Curik, Jan Zach, Martin Novak, Iuri Marinov, Simona Soverini, Edgar Faber, Katerina Machova Polakova
Format:	Article
Language:	English
Published:	Public Library of Science (PLoS) 2016-01-01
Series:	PLoS ONE
Online Access:	http://europepmc.org/articles/PMC4877000?pdf=render

id	doaj-eec7181a37d04b6a995c86b77927b702
record_format	Article
spelling	doaj-eec7181a37d04b6a995c86b77927b7022020-11-24T21:52:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015595910.1371/journal.pone.0155959Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.Vaclava PolivkovaPeter RohonHana KlamovaOlga CernaMartina DivokaNikola CurikJan ZachMartin NovakIuri MarinovSimona SoveriniEdgar FaberKaterina Machova PolakovaBone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy.http://europepmc.org/articles/PMC4877000?pdf=render
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Vaclava Polivkova Peter Rohon Hana Klamova Olga Cerna Martina Divoka Nikola Curik Jan Zach Martin Novak Iuri Marinov Simona Soverini Edgar Faber Katerina Machova Polakova
spellingShingle	Vaclava Polivkova Peter Rohon Hana Klamova Olga Cerna Martina Divoka Nikola Curik Jan Zach Martin Novak Iuri Marinov Simona Soverini Edgar Faber Katerina Machova Polakova Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients. PLoS ONE
author_facet	Vaclava Polivkova Peter Rohon Hana Klamova Olga Cerna Martina Divoka Nikola Curik Jan Zach Martin Novak Iuri Marinov Simona Soverini Edgar Faber Katerina Machova Polakova
author_sort	Vaclava Polivkova
title	Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.
title_short	Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.
title_full	Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.
title_fullStr	Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.
title_full_unstemmed	Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.
title_sort	interferon-α revisited: individualized treatment management eased the selective pressure of tyrosine kinase inhibitors on bcr-abl1 mutations resulting in a molecular response in high-risk cml patients.
publisher	Public Library of Science (PLoS)
series	PLoS ONE
issn	1932-6203
publishDate	2016-01-01
description	Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy.
url	http://europepmc.org/articles/PMC4877000?pdf=render
work_keys_str_mv	AT vaclavapolivkova interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT peterrohon interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT hanaklamova interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT olgacerna interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT martinadivoka interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT nikolacurik interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT janzach interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT martinnovak interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT iurimarinov interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT simonasoverini interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT edgarfaber interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients AT katerinamachovapolakova interferonarevisitedindividualizedtreatmentmanagementeasedtheselectivepressureoftyrosinekinaseinhibitorsonbcrabl1mutationsresultinginamolecularresponseinhighriskcmlpatients
_version_	1725876342693560320

Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

Similar Items