Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients
Abstract Antiapoptotic Bcl‐2 family proteins are involved in myeloma cell survival. To date, their expression in multiple myeloma (MM) patients has mostly been analyzed at the RNA level. In the present study, we quantified for the first time the protein expression of the Bcl2‐family members using a...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | HemaSphere |
| Online Access: | https://doi.org/10.1002/hem3.70036 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556250940145664 |
|---|---|
| author | Cristina De Ramón Elizabeta A. Rojas Irena Misiewicz‐Krzeminska Ignacio J. Cardona‐Benavides Myriam Cuadrado Isabel Isidro María‐José Calasanz Manuela Fernandez Ramón García‐Sanz Noemi Puig M. Teresa Cedena Bruno Paiva Laura Rosiñol Joaquín Martínez‐López Joan Bladé Juan J. Lahuerta Jesús F. San Miguel María V. Mateos Luis A. Corchete Norma C. Gutiérrez GEM/PETHEMA cooperative study group |
| author_facet | Cristina De Ramón Elizabeta A. Rojas Irena Misiewicz‐Krzeminska Ignacio J. Cardona‐Benavides Myriam Cuadrado Isabel Isidro María‐José Calasanz Manuela Fernandez Ramón García‐Sanz Noemi Puig M. Teresa Cedena Bruno Paiva Laura Rosiñol Joaquín Martínez‐López Joan Bladé Juan J. Lahuerta Jesús F. San Miguel María V. Mateos Luis A. Corchete Norma C. Gutiérrez GEM/PETHEMA cooperative study group |
| author_sort | Cristina De Ramón |
| collection | DOAJ |
| description | Abstract Antiapoptotic Bcl‐2 family proteins are involved in myeloma cell survival. To date, their expression in multiple myeloma (MM) patients has mostly been analyzed at the RNA level. In the present study, we quantified for the first time the protein expression of the Bcl2‐family members using a capillary electrophoresis immunoassay in 120 newly diagnosed MM patients, aged ≤65 years, treated in the context of the PETHEMA/GEM2012 study. We found that the pattern of expression of Bcl‐2 family proteins was highly heterogeneous among patients. Although cases with t(11;14) had significantly higher levels of Bcl‐2/Bcl‐xL and Bcl‐2+Bim+Bax/Bcl‐xL ratios than those without t(11;14), the presence of this translocation was not synonymous with such high levels of expression. Conversely, some patients with other genetic alterations also showed higher levels of those ratios. Survival analysis revealed that the high expression of Bad and Puma proteins was associated with significantly longer overall survival (p = 0.001 and p < 0.001, respectively). Bcl‐2 protein ratios predicting sensitivity to venetoclax in vitro were also able to distinguish patients with shorter time to progression after triplet‐based induction therapy and ASCT. This is the first study to assess the expression of the most important Bcl‐2 family proteins by a quantitative method in a large set of MM patients according to their cytogenetic abnormalities. We shed light on the impact of these proteins on MM prognosis, which could help to consider the levels of proteins involved in apoptosis in the development of new therapeutic strategies. |
| format | Article |
| id | doaj-art-f47b6261bd984f60a623d2b3ec6b372d |
| institution | Kabale University |
| issn | 2572-9241 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj-art-f47b6261bd984f60a623d2b3ec6b372d2025-01-07T12:35:28ZengWileyHemaSphere2572-92412024-12-01812n/an/a10.1002/hem3.70036Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patientsCristina De Ramón0Elizabeta A. Rojas1Irena Misiewicz‐Krzeminska2Ignacio J. Cardona‐Benavides3Myriam Cuadrado4Isabel Isidro5María‐José Calasanz6Manuela Fernandez7Ramón García‐Sanz8Noemi Puig9M. Teresa Cedena10Bruno Paiva11Laura Rosiñol12Joaquín Martínez‐López13Joan Bladé14Juan J. Lahuerta15Jesús F. San Miguel16María V. Mateos17Luis A. Corchete18Norma C. Gutiérrez19GEM/PETHEMA cooperative study groupDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Experimental Hematology Institute of Hematology and Transfusion Medicine Warsaw PolandDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology Clínica Universidad de Navarra, Centro de Investigaciones Biomédicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona SpainSpanish National Cancer Research Center (CNIO) Madrid SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainSpanish National Cancer Research Center (CNIO) Madrid SpainDepartment of Hematology Clínica Universidad de Navarra, Centro de Investigaciones Biomédicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona SpainDepartment of Hematology Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS) Barcelona SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC)Department of Hematology Hospital Clinic of Barcelona, Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS) Barcelona SpainDepartment of Hematology University Hospital 12 de Octubre Madrid SpainDepartment of Hematology Clínica Universidad de Navarra, Centro de Investigaciones Biomédicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainDepartment of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca SpainAbstract Antiapoptotic Bcl‐2 family proteins are involved in myeloma cell survival. To date, their expression in multiple myeloma (MM) patients has mostly been analyzed at the RNA level. In the present study, we quantified for the first time the protein expression of the Bcl2‐family members using a capillary electrophoresis immunoassay in 120 newly diagnosed MM patients, aged ≤65 years, treated in the context of the PETHEMA/GEM2012 study. We found that the pattern of expression of Bcl‐2 family proteins was highly heterogeneous among patients. Although cases with t(11;14) had significantly higher levels of Bcl‐2/Bcl‐xL and Bcl‐2+Bim+Bax/Bcl‐xL ratios than those without t(11;14), the presence of this translocation was not synonymous with such high levels of expression. Conversely, some patients with other genetic alterations also showed higher levels of those ratios. Survival analysis revealed that the high expression of Bad and Puma proteins was associated with significantly longer overall survival (p = 0.001 and p < 0.001, respectively). Bcl‐2 protein ratios predicting sensitivity to venetoclax in vitro were also able to distinguish patients with shorter time to progression after triplet‐based induction therapy and ASCT. This is the first study to assess the expression of the most important Bcl‐2 family proteins by a quantitative method in a large set of MM patients according to their cytogenetic abnormalities. We shed light on the impact of these proteins on MM prognosis, which could help to consider the levels of proteins involved in apoptosis in the development of new therapeutic strategies.https://doi.org/10.1002/hem3.70036 |
| spellingShingle | Cristina De Ramón Elizabeta A. Rojas Irena Misiewicz‐Krzeminska Ignacio J. Cardona‐Benavides Myriam Cuadrado Isabel Isidro María‐José Calasanz Manuela Fernandez Ramón García‐Sanz Noemi Puig M. Teresa Cedena Bruno Paiva Laura Rosiñol Joaquín Martínez‐López Joan Bladé Juan J. Lahuerta Jesús F. San Miguel María V. Mateos Luis A. Corchete Norma C. Gutiérrez GEM/PETHEMA cooperative study group Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients HemaSphere |
| title | Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients |
| title_full | Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients |
| title_fullStr | Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients |
| title_full_unstemmed | Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients |
| title_short | Expression profile of Bcl‐2 family proteins in newly diagnosed multiple myeloma patients |
| title_sort | expression profile of bcl 2 family proteins in newly diagnosed multiple myeloma patients |
| url | https://doi.org/10.1002/hem3.70036 |
| work_keys_str_mv | AT cristinaderamon expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT elizabetaarojas expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT irenamisiewiczkrzeminska expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT ignaciojcardonabenavides expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT myriamcuadrado expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT isabelisidro expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT mariajosecalasanz expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT manuelafernandez expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT ramongarciasanz expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT noemipuig expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT mteresacedena expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT brunopaiva expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT laurarosinol expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT joaquinmartinezlopez expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT joanblade expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT juanjlahuerta expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT jesusfsanmiguel expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT mariavmateos expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT luisacorchete expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT normacgutierrez expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients AT gempethemacooperativestudygroup expressionprofileofbcl2familyproteinsinnewlydiagnosedmultiplemyelomapatients |