Genomic Landscape of Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Central Study.

Fei, Fei; Jariwala, Amar; Pullarkat, Sheeja; Loo, Eric; Liu, Yan; Tizro, Parastou; Ali, Haris; Otoukesh, Salman; Amanam, Idoroenyi; Artz, Andrew; Ally, Feras; Telatar, Milhan; Nakamura, Ryotaro; Marcucci, Guido; Afkhami, Michelle

Fei, Fei; Jariwala, Amar; Pullarkat, Sheeja; Loo, Eric; Liu, Yan; Tizro, Parastou; Ali, Haris; Otoukesh, Salman; Amanam, Idoroenyi; Artz, Andrew; Ally, Feras; Telatar, Milhan; Nakamura, Ryotaro; Marcucci, Guido; Afkhami, Michelle.

Afiliação

Fei F; Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Jariwala A; Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Pullarkat S; Fulgent Oncology, 4399 Santa Anita Ave, El Monte, CA 91731, USA.
Loo E; Department of Pathology, Division of Hematopathology, University of Los Angeles Medical Center, Los Angeles, CA 90095, USA.
Liu Y; Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Tizro P; Department of Pathology and Laboratory Medicine, Loma Linda University Health, Loma Linda, CA 92350, USA.
Ali H; Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Otoukesh S; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Amanam I; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Artz A; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Ally F; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Telatar M; Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA.
Nakamura R; Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Marcucci G; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Afkhami M; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.

Int J Mol Sci ; 25(18)2024 Sep 23.

Article em En | MEDLINE | ID: mdl-39337700

ABSTRACT

ABSTRACT

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

Assuntos

Mutação; Doenças Mieloproliferativas-Mielodisplásicas; Proteínas Proto-Oncogênicas; Humanos; Idoso; Masculino; Feminino; Pessoa de Meia-Idade; Doenças Mieloproliferativas-Mielodisplásicas/genética; Doenças Mieloproliferativas-Mielodisplásicas/classificação; Idoso de 80 Anos ou mais; Proteínas Proto-Oncogênicas/genética; Adulto; Dioxigenases; Fatores de Processamento de Serina-Arginina/genética; Janus Quinase 2/genética; Proteínas de Ligação a DNA/genética; Genômica/métodos; Leucemia Mielomonocítica Crônica/genética; Leucemia Mielomonocítica Crônica/patologia; Síndromes Mielodisplásicas/genética; Subunidade alfa 2 de Fator de Ligação ao Core/genética; Transtornos Mieloproliferativos/genética; Transtornos Mieloproliferativos/diagnóstico; Proteínas Repressoras/genética; Fatores de Processamento de RNA/genética; Proteínas de Transporte; Proteínas Nucleares

Palavras-chave

gene mutation; genomic; myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN); myeloid neoplasm; next-generation sequencing

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas / Doenças Mieloproliferativas-Mielodisplásicas / Mutação Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Suíça

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