ChloroquineV1, France, Analysis, bibRecord, 000056

Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death

Identifieur interne : 000056 ( France/Analysis ); précédent : 000055; suivant : 000057

Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death

Auteurs : Avedis Torossian [France] ; Nicolas Broin [France] ; Julie Frentzel [France] ; Camille Daugrois [France] ; Sarah Gandarillas [France] ; Talal Al Saati [France] ; Laurence Lamant [France, Royaume-Uni] ; Pierre Brousset [France, Royaume-Uni] ; Sylvie Giuriato [France, Royaume-Uni, Belgique] ; Estelle Espinos [France, Royaume-Uni]

Source :

Haematologica [ 0390-6078 ] ; 2019.

RBID : PMC:6601090

Abstract

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas are tumors that carry translocations involving the ALK gene at the 2p23 locus, leading to the expression of ALK tyrosine kinase fusion oncoproteins. Amongst hematologic malignancies, these lymphomas are particular in that they express very low levels of B-cell lymphoma 2 (BCL2), a recognized inhibitor of apoptosis and autophagy, two processes that share complex interconnections. We have previously shown that treatment of ALK-positive anaplastic large cell lymphoma cells with the ALK tyrosine kinase inhibitor crizotinib induces autophagy as a pro-survival response. Here, we observed that crizotinib-mediated inactivation of ALK caused an increase in BCL2 levels that restrained the cytotoxic effects of the drug. BCL2 downregulation in combination with crizotinib treatment potentiated loss of cell viability through both an increase in autophagic flux and cell death, including apoptosis. More importantly, our data revealed that the blockade of autophagic flux completely reversed impaired cell viability, which demonstrates that excessive autophagy is associated with cell death. We propose that the downregulation of BCL2 protein, which plays a central role in the autophagic and apoptotic machinery, combined with crizotinib treatment may represent a promising therapeutic alternative to current ALK-positive anaplastic large cell lymphoma treatments.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601090

DOI: 10.3324/haematol.2017.181966
PubMed: 30679328
PubMed Central: 6601090

Affiliations:

Links to Exploration step

PMC:6601090

Le document en format XML

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<author><name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
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<affiliation wicri:level="3"><nlm:aff id="af4-1041428">Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af8-1041428">European Research Initiative on ALK-related Malignancies (ERIA), Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>European Research Initiative on ALK-related Malignancies (ERIA), Cambridge</wicri:regionArea>
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<idno type="wicri:doubleKey">0390-6078:2019:Torossian A:blockade:of:crizotinib</idno>
<idno type="wicri:Area/Main/Merge">000992</idno>
<idno type="wicri:Area/Main/Curation">000992</idno>
<idno type="wicri:Area/Main/Exploration">000992</idno>
<idno type="wicri:Area/France/Extraction">000056</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death</title>
<author><name sortKey="Torossian, Avedis" sort="Torossian, Avedis" uniqKey="Torossian A" first="Avedis" last="Torossian">Avedis Torossian</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Broin, Nicolas" sort="Broin, Nicolas" uniqKey="Broin N" first="Nicolas" last="Broin">Nicolas Broin</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Frentzel, Julie" sort="Frentzel, Julie" uniqKey="Frentzel J" first="Julie" last="Frentzel">Julie Frentzel</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Daugrois, Camille" sort="Daugrois, Camille" uniqKey="Daugrois C" first="Camille" last="Daugrois">Camille Daugrois</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af4-1041428">Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gandarillas, Sarah" sort="Gandarillas, Sarah" uniqKey="Gandarillas S" first="Sarah" last="Gandarillas">Sarah Gandarillas</name>
<affiliation wicri:level="3"><nlm:aff id="af5-1041428">Inserm/UPS, US006/CREFRE, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm/UPS, US006/CREFRE, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Saati, Talal Al" sort="Saati, Talal Al" uniqKey="Saati T" first="Talal Al" last="Saati">Talal Al Saati</name>
<affiliation wicri:level="3"><nlm:aff id="af6-1041428">Inserm/UPS, US006/CREFRE, Service d’Histopathologie, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm/UPS, US006/CREFRE, Service d’Histopathologie, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af4-1041428">Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af7-1041428">Département de Pathologie, IUCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Département de Pathologie, IUCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8-1041428">European Research Initiative on ALK-related Malignancies (ERIA), Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>European Research Initiative on ALK-related Malignancies (ERIA), Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af4-1041428">Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af7-1041428">Département de Pathologie, IUCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Département de Pathologie, IUCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8-1041428">European Research Initiative on ALK-related Malignancies (ERIA), Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>European Research Initiative on ALK-related Malignancies (ERIA), Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Giuriato, Sylvie" sort="Giuriato, Sylvie" uniqKey="Giuriato S" first="Sylvie" last="Giuriato">Sylvie Giuriato</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8-1041428">European Research Initiative on ALK-related Malignancies (ERIA), Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>European Research Initiative on ALK-related Malignancies (ERIA), Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af9-1041428">Transautophagy: European network for multidisciplinary research and translation of autophagy knowledge, COST Action CA15138, Brussel, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Transautophagy: European network for multidisciplinary research and translation of autophagy knowledge, COST Action CA15138, Brussel</wicri:regionArea>
<wicri:noRegion>Brussel</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
<affiliation wicri:level="3"><nlm:aff id="af1-1041428">Inserm, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af2-1041428">Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af3-1041428">CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, ERL5294 UMR1037 CRCT, F-31000, Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="af4-1041428">Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire d’Excellence Toulouse-Cancer-TOUCAN, F-31024 Toulouse</wicri:regionArea>
<placeName><region type="region" nuts="2">Occitanie (région administrative)</region>
<region type="old region" nuts="2">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8-1041428">European Research Initiative on ALK-related Malignancies (ERIA), Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>European Research Initiative on ALK-related Malignancies (ERIA), Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Haematologica</title>
<idno type="ISSN">0390-6078</idno>
<idno type="eISSN">1592-8721</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas are tumors that carry translocations involving the <italic>ALK</italic>
 gene at the 2p23 locus, leading to the expression of ALK tyrosine kinase fusion oncoproteins. Amongst hematologic malignancies, these lymphomas are particular in that they express very low levels of B-cell lymphoma 2 (BCL2), a recognized inhibitor of apoptosis and autophagy, two processes that share complex interconnections. We have previously shown that treatment of ALK-positive anaplastic large cell lymphoma cells with the ALK tyrosine kinase inhibitor crizotinib induces autophagy as a pro-survival response. Here, we observed that crizotinib-mediated inactivation of ALK caused an increase in BCL2 levels that restrained the cytotoxic effects of the drug. BCL2 downregulation in combination with crizotinib treatment potentiated loss of cell viability through both an increase in autophagic flux and cell death, including apoptosis. More importantly, our data revealed that the blockade of autophagic flux completely reversed impaired cell viability, which demonstrates that excessive autophagy is associated with cell death. We propose that the downregulation of BCL2 protein, which plays a central role in the autophagic and apoptotic machinery, combined with crizotinib treatment may represent a promising therapeutic alternative to current ALK-positive anaplastic large cell lymphoma treatments.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Turner, Sd" uniqKey="Turner S">SD Turner</name>
</author>
<author><name sortKey="Lamant, L" uniqKey="Lamant L">L Lamant</name>
</author>
<author><name sortKey="Kenner, L" uniqKey="Kenner L">L Kenner</name>
</author>
<author><name sortKey="Brugieres, L" uniqKey="Brugieres L">L Brugières</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Swerdlow, Sh" uniqKey="Swerdlow S">SH Swerdlow</name>
</author>
<author><name sortKey="Campo, E" uniqKey="Campo E">E Campo</name>
</author>
<author><name sortKey="Pileri, Sa" uniqKey="Pileri S">SA Pileri</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morris, Sw" uniqKey="Morris S">SW Morris</name>
</author>
<author><name sortKey="Kirstein, Mn" uniqKey="Kirstein M">MN Kirstein</name>
</author>
<author><name sortKey="Valentine, Mb" uniqKey="Valentine M">MB Valentine</name>
</author>
</analytic>
</biblStruct>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Belgique</li>
<li>France</li>
<li>Royaume-Uni</li>
</country>
<region><li>Midi-Pyrénées</li>
<li>Occitanie (région administrative)</li>
</region>
<settlement><li>Toulouse</li>
</settlement>
</list>
<tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Torossian, Avedis" sort="Torossian, Avedis" uniqKey="Torossian A" first="Avedis" last="Torossian">Avedis Torossian</name>
</region>
<name sortKey="Broin, Nicolas" sort="Broin, Nicolas" uniqKey="Broin N" first="Nicolas" last="Broin">Nicolas Broin</name>
<name sortKey="Broin, Nicolas" sort="Broin, Nicolas" uniqKey="Broin N" first="Nicolas" last="Broin">Nicolas Broin</name>
<name sortKey="Broin, Nicolas" sort="Broin, Nicolas" uniqKey="Broin N" first="Nicolas" last="Broin">Nicolas Broin</name>
<name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<name sortKey="Daugrois, Camille" sort="Daugrois, Camille" uniqKey="Daugrois C" first="Camille" last="Daugrois">Camille Daugrois</name>
<name sortKey="Daugrois, Camille" sort="Daugrois, Camille" uniqKey="Daugrois C" first="Camille" last="Daugrois">Camille Daugrois</name>
<name sortKey="Daugrois, Camille" sort="Daugrois, Camille" uniqKey="Daugrois C" first="Camille" last="Daugrois">Camille Daugrois</name>
<name sortKey="Daugrois, Camille" sort="Daugrois, Camille" uniqKey="Daugrois C" first="Camille" last="Daugrois">Camille Daugrois</name>
<name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
<name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
<name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
<name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
<name sortKey="Frentzel, Julie" sort="Frentzel, Julie" uniqKey="Frentzel J" first="Julie" last="Frentzel">Julie Frentzel</name>
<name sortKey="Frentzel, Julie" sort="Frentzel, Julie" uniqKey="Frentzel J" first="Julie" last="Frentzel">Julie Frentzel</name>
<name sortKey="Frentzel, Julie" sort="Frentzel, Julie" uniqKey="Frentzel J" first="Julie" last="Frentzel">Julie Frentzel</name>
<name sortKey="Gandarillas, Sarah" sort="Gandarillas, Sarah" uniqKey="Gandarillas S" first="Sarah" last="Gandarillas">Sarah Gandarillas</name>
<name sortKey="Giuriato, Sylvie" sort="Giuriato, Sylvie" uniqKey="Giuriato S" first="Sylvie" last="Giuriato">Sylvie Giuriato</name>
<name sortKey="Giuriato, Sylvie" sort="Giuriato, Sylvie" uniqKey="Giuriato S" first="Sylvie" last="Giuriato">Sylvie Giuriato</name>
<name sortKey="Giuriato, Sylvie" sort="Giuriato, Sylvie" uniqKey="Giuriato S" first="Sylvie" last="Giuriato">Sylvie Giuriato</name>
<name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
<name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
<name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
<name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
<name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
<name sortKey="Saati, Talal Al" sort="Saati, Talal Al" uniqKey="Saati T" first="Talal Al" last="Saati">Talal Al Saati</name>
<name sortKey="Torossian, Avedis" sort="Torossian, Avedis" uniqKey="Torossian A" first="Avedis" last="Torossian">Avedis Torossian</name>
<name sortKey="Torossian, Avedis" sort="Torossian, Avedis" uniqKey="Torossian A" first="Avedis" last="Torossian">Avedis Torossian</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Lamant, Laurence" sort="Lamant, Laurence" uniqKey="Lamant L" first="Laurence" last="Lamant">Laurence Lamant</name>
</noRegion>
<name sortKey="Brousset, Pierre" sort="Brousset, Pierre" uniqKey="Brousset P" first="Pierre" last="Brousset">Pierre Brousset</name>
<name sortKey="Espinos, Estelle" sort="Espinos, Estelle" uniqKey="Espinos E" first="Estelle" last="Espinos">Estelle Espinos</name>
<name sortKey="Giuriato, Sylvie" sort="Giuriato, Sylvie" uniqKey="Giuriato S" first="Sylvie" last="Giuriato">Sylvie Giuriato</name>
</country>
<country name="Belgique"><noRegion><name sortKey="Giuriato, Sylvie" sort="Giuriato, Sylvie" uniqKey="Giuriato S" first="Sylvie" last="Giuriato">Sylvie Giuriato</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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{{Explor lien
   |wiki=    Sante
   |area=    ChloroquineV1
   |flux=    France
   |étape=   Analysis
   |type=    RBID
   |clé=     PMC:6601090
   |texte=   Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death
}}

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HfdIndexSelect -h $EXPLOR_AREA/Data/France/Analysis/RBID.i   -Sk "pubmed:30679328" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/France/Analysis/biblio.hfd   \
       | NlmPubMed2Wicri -a ChloroquineV1

This area was generated with Dilib version V0.6.33.
Data generation: Wed Mar 25 22:43:59 2020. Site generation: Sun Jan 31 12:44:45 2021

Serveur d'exploration Chloroquine

Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death

Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death

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Abstract

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	Serveur d'exploration Chloroquine
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.