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Influence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletion.
Montoro, Maria Julia; Palomo, Laura; Haferlach, Claudia; Acha, Pamela; Chan, Onyee; Navarro, Víctor; Kubota, Yasuo; Schulz, Felicitas Isabel; Meggendorfer, Manja; Briski, Robert; Al Ali, Najla; Xicoy, Blanca; López-Cadenas, Félix; Bosch, Francesc; González, Teresa; Eder, Lea Naomi; Jerez, Andrés; Wang, Yu-Hung; Campagna, Alessia; Santini, Valeria; Bernal Del Castillo, Teresa; Such, Esperanza; Tien, Hwei-Fang; Diaz Varela, Nicolás; Platzbecker, Uwe; Haase, Detlef; Díez-Campelo, María; Della Porta, Matteo; Garcia-Manero, Guillermo; Wiseman, Daniel H; Germing, Ulrich; Maciejewski, Jaroslaw P; Komrokji, Rami S; Sole, Francesc; Haferlach, Torsten; Valcárcel, David.
Afiliação
  • Montoro MJ; Department of Hematology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Palomo L; Department of Hematology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Haferlach C; MLL Munich Leukemia Laboratory, Munich, Germany.
  • Acha P; MDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, Badalona, Spain.
  • Chan O; Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL.
  • Navarro V; Oncology Data Science Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Kubota Y; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
  • Schulz FI; Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, University Hospital of Düsseldorf, Düsseldorf, Germany.
  • Meggendorfer M; MLL Munich Leukemia Laboratory, Munich, Germany.
  • Briski R; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.
  • Al Ali N; Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL.
  • Xicoy B; MDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, Badalona, Spain.
  • López-Cadenas F; Department of Hematology, Hospital del Mar, Barcelona, Spain.
  • Bosch F; Department of Hematology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • González T; Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
  • Eder LN; Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Georg August University, Göttingen, Germany.
  • Jerez A; Department of Hematology, Hospital Morales Meseguer, Murcia, Spain.
  • Wang YH; Division of Cancer Sciences, Epigenetics of Haematopoiesis Laboratory, The University of Manchester, Manchester, United Kingdom.
  • Campagna A; Department of Biomedical Sciences, Humanitas Clinical and Research Center-IRCCS and Humanitas University, Milan, Italy.
  • Santini V; Hematology, MDS Unit, University of Florence, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
  • Bernal Del Castillo T; Department of Hematology, Servicio de Hematología, Hospital Universitario Central de Asturias Instituto de Investigación del Principado de Asturias, Oviedo, Spain.
  • Such E; Department of Hematology, Servicio de Hematología, Hospital La Fe, Valencia, Spain.
  • Tien HF; Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Diaz Varela N; Department of Hematology, Servicio de Hematología, Hospital Universitario Central de Asturias Instituto de Investigación del Principado de Asturias, Oviedo, Spain.
  • Platzbecker U; Department of Hematology, University Hospital of Leipzig, Dresden, Germany.
  • Haase D; Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Georg August University, Göttingen, Germany.
  • Díez-Campelo M; Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
  • Della Porta M; Department of Biomedical Sciences, Humanitas Clinical and Research Center-IRCCS and Humanitas University, Milan, Italy.
  • Garcia-Manero G; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.
  • Wiseman DH; Division of Cancer Sciences, Epigenetics of Haematopoiesis Laboratory, The University of Manchester, Manchester, United Kingdom.
  • Germing U; Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, University Hospital of Düsseldorf, Düsseldorf, Germany.
  • Maciejewski JP; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
  • Komrokji RS; Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL.
  • Sole F; MDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, Badalona, Spain.
  • Haferlach T; MLL Munich Leukemia Laboratory, Munich, Germany.
  • Valcárcel D; Department of Hematology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Blood ; 144(16): 1722-1731, 2024 Oct 17.
Article em En | MEDLINE | ID: mdl-39074355
ABSTRACT
ABSTRACT Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, whereas the remaining patients displayed monoallelic mutations. TP53-multihit alterations were predictive of an increased risk of leukemic transformation. The impact of monoallelic alterations was dependent on the variant allele frequency (VAF); patients with TP53-monoallelic mutations and VAF <20% exhibited behavior similar to TP53 wild type, and those with TP53-monoallelic mutations and VAF ≥20% presented outcomes equivalent to TP53-multihit patients. This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndromes Mielodisplásicas / Cromossomos Humanos Par 5 / Proteína Supressora de Tumor p53 / Deleção Cromossômica Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndromes Mielodisplásicas / Cromossomos Humanos Par 5 / Proteína Supressora de Tumor p53 / Deleção Cromossômica Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha