ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy.
Resistance to Imatinib Mesylate (IM) is a major problem in Chronic Myelogenous Leukaemia management. Most of the studies about resistance have focused on point mutations on BCR/ABL. However, other types of resistance that do not imply mutations in BCR/ABL have been also described. In the present rep...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2009
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/3dff57472bb442969456148bb3804193 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:3dff57472bb442969456148bb3804193 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:3dff57472bb442969456148bb38041932021-11-25T06:21:48ZERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy.1932-620310.1371/journal.pone.0006124https://doaj.org/article/3dff57472bb442969456148bb38041932009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19568437/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Resistance to Imatinib Mesylate (IM) is a major problem in Chronic Myelogenous Leukaemia management. Most of the studies about resistance have focused on point mutations on BCR/ABL. However, other types of resistance that do not imply mutations in BCR/ABL have been also described. In the present report we aim to study the role of several MAPK in IM resistance not associate to BCR/ABL mutations. Therefore we used an experimental system of resistant cell lines generated by co-culturing with IM (K562, Lama 84) as well as primary material from resistant and responder patient without BCR/ABL mutations. Here we demonstrate that Erk5 and p38MAPK signaling pathways are not implicated in the acquired resistance phenotype. However, Erk2, but not Erk1, is critical for the acquired resistance to IM. In fact, Bcr/Abl activates preferentially Erk2 in transient transfection in a dose dependent fashion through the c-Abl part of the chimeric protein. Finally, we present evidences demonstrating how constitutive activation of Erk2 is a de novo mechanism of resistance to IM. In summary our data support the use of therapeutic approaches based on Erk2 inhibition, which could be added to the therapeutic armamentarium to fight CML, especially when IM resistance develops secondary to Erk2 activation.Clara I Aceves-LuqueroAnupriya AgarwalJuan L Callejas-ValeraLaura Arias-GonzálezAzucena Esparís-OgandoLuis del Peso OvalleItxaso Bellón-EcheverriaMiguel A de la Cruz-MorcilloEva M Galán MoyaInmaculada Moreno GimenoJuan C GómezMichael W DeiningerAtanasio PandiellaRicardo Sánchez PrietoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 7, p e6124 (2009) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Clara I Aceves-Luquero Anupriya Agarwal Juan L Callejas-Valera Laura Arias-González Azucena Esparís-Ogando Luis del Peso Ovalle Itxaso Bellón-Echeverria Miguel A de la Cruz-Morcillo Eva M Galán Moya Inmaculada Moreno Gimeno Juan C Gómez Michael W Deininger Atanasio Pandiella Ricardo Sánchez Prieto ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. |
| description |
Resistance to Imatinib Mesylate (IM) is a major problem in Chronic Myelogenous Leukaemia management. Most of the studies about resistance have focused on point mutations on BCR/ABL. However, other types of resistance that do not imply mutations in BCR/ABL have been also described. In the present report we aim to study the role of several MAPK in IM resistance not associate to BCR/ABL mutations. Therefore we used an experimental system of resistant cell lines generated by co-culturing with IM (K562, Lama 84) as well as primary material from resistant and responder patient without BCR/ABL mutations. Here we demonstrate that Erk5 and p38MAPK signaling pathways are not implicated in the acquired resistance phenotype. However, Erk2, but not Erk1, is critical for the acquired resistance to IM. In fact, Bcr/Abl activates preferentially Erk2 in transient transfection in a dose dependent fashion through the c-Abl part of the chimeric protein. Finally, we present evidences demonstrating how constitutive activation of Erk2 is a de novo mechanism of resistance to IM. In summary our data support the use of therapeutic approaches based on Erk2 inhibition, which could be added to the therapeutic armamentarium to fight CML, especially when IM resistance develops secondary to Erk2 activation. |
| format |
article |
| author |
Clara I Aceves-Luquero Anupriya Agarwal Juan L Callejas-Valera Laura Arias-González Azucena Esparís-Ogando Luis del Peso Ovalle Itxaso Bellón-Echeverria Miguel A de la Cruz-Morcillo Eva M Galán Moya Inmaculada Moreno Gimeno Juan C Gómez Michael W Deininger Atanasio Pandiella Ricardo Sánchez Prieto |
| author_facet |
Clara I Aceves-Luquero Anupriya Agarwal Juan L Callejas-Valera Laura Arias-González Azucena Esparís-Ogando Luis del Peso Ovalle Itxaso Bellón-Echeverria Miguel A de la Cruz-Morcillo Eva M Galán Moya Inmaculada Moreno Gimeno Juan C Gómez Michael W Deininger Atanasio Pandiella Ricardo Sánchez Prieto |
| author_sort |
Clara I Aceves-Luquero |
| title |
ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. |
| title_short |
ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. |
| title_full |
ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. |
| title_fullStr |
ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. |
| title_full_unstemmed |
ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy. |
| title_sort |
erk2, but not erk1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for cml therapy. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/3dff57472bb442969456148bb3804193 |
| work_keys_str_mv |
AT claraiacevesluquero erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT anupriyaagarwal erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT juanlcallejasvalera erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT lauraariasgonzalez erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT azucenaesparisogando erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT luisdelpesoovalle erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT itxasobellonecheverria erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT migueladelacruzmorcillo erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT evamgalanmoya erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT inmaculadamorenogimeno erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT juancgomez erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT michaelwdeininger erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT atanasiopandiella erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy AT ricardosanchezprieto erk2butnoterk1mediatesacquiredanddenovoresistancetoimatinibmesylateimplicationforcmltherapy |
| _version_ |
1718413797211766784 |