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Genomic and global gene expression profiling in pediatric and young adult acute leukemia with PICALM::MLLT10 Fusion.
Ma, Jingqun; Liu, Yen-Chun; Voss, Rebecca K; Ma, Jing; Palagani, Ajay; Caldwell, Elizabeth; Rosikiewicz, Wojciech; Cardenas, Maria; Foy, Scott; Umeda, Masayuki; Wilkinson, Mark R; Inaba, Hiroto; Klco, Jeffery M; Rubnitz, Jeffrey E; Wang, Lu.
Afiliación
  • Ma J; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Liu YC; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Voss RK; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Ma J; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Palagani A; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Caldwell E; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Rosikiewicz W; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Cardenas M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Foy S; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Umeda M; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Wilkinson MR; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Inaba H; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Klco JM; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Rubnitz JE; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Wang L; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. Lu.Wang2@stjude.org.
Leukemia ; 38(5): 981-990, 2024 May.
Article en En | MEDLINE | ID: mdl-38429501
ABSTRACT
PICALM MLLT10 fusion is a rare but recurrent genetic driver in acute leukemias. To better understand the genomic landscape of PICALMMLLT10 (PM) positive acute leukemia, we performed genomic profiling and gene expression profiling in twenty PM-positive patients, including AML (n = 10), T-ALL/LLy (n = 8), Mixed-phenotype acute leukemia (MPAL), T/B (n = 1) and acute undifferentiated leukemia (AUL) (n = 1). Besides confirming the known activation of HOXA, differential gene expression analysis compared to hematopoietic stem cells demonstrated the enrichment of genes associated with cell proliferation-related pathways and relatively high expression of XPO1 in PM-AML and PM-T-ALL/LLy. Our study also suggested PHF6 disruption as a key cooperating event in PICALMMLLT10-positive leukemias. In addition, we demonstrated differences in gene expression profiles as well as remarkably different spectra of co-occurring mutations between PM-AML and PM-T-ALL/LLy. Alterations affecting TP53 and NF1, hallmarks of PM-AML, are strongly associated with disease progression and relapse, whereas EZH2 alterations are highly enriched in PM-T-ALL/LLy. This comprehensive genomic and transcriptomic profiling provides insights into the pathogenesis and development of PICALMMLLT10 positive acute leukemia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Fusión Oncogénica / Perfilación de la Expresión Génica Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Fusión Oncogénica / Perfilación de la Expresión Génica Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido