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Bilineal evolution of a U2AF1-mutated clone associated with acquisition of distinct secondary mutations.
Montgomery, Nathan D; Galeotti, Jonathan; Johnson, Steven M; Commander, Leah; Weimer, Eric T; Chandra, Pranil K; Nazir, Tariq; Alexander, Thomas B; Zeidner, Joshua F; Foster, Matthew C.
Afiliación
  • Montgomery ND; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Galeotti J; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Johnson SM; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Commander L; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Weimer ET; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Chandra PK; PathGroup, Nashville, TN.
  • Nazir T; Cape Fear Valley Cancer Treatment Center, Fayetteville, NC and.
  • Alexander TB; Division of Pediatric Oncology, Department of Pediatrics, and.
  • Zeidner JF; Division of Hematology and Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Foster MC; Division of Hematology and Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Blood Adv ; 5(24): 5612-5616, 2021 12 28.
Article en En | MEDLINE | ID: mdl-34581783
Rare hematologic malignancies display evidence of both myeloid and lymphoid differentiation. Here, we describe such a novel bilineal event discovered in an adult woman with B-lymphoblastic leukemia (BLL). At the time of BLL diagnosis, the patient had a normal karyotype and a bulk sequencing panel identified pathogenic variants in BCOR, EZH2, RUNX1, and U2AF1, a genotype more typical of myeloid neoplasia. Additionally, the patient was noted to have 3-year history of cytopenias, and morphologic dyspoiesis was noted on post-treatment samples, raising the possibility of an antecedent hematologic disorder. To investigate the clonal architecture of her disease, we performed targeted sequencing on fractionated samples enriched for either B-lymphoblasts or circulating granulocytes. These studies revealed a truncal founder mutation in the spliceosome gene U2AF1 in both fractions, while distinct secondary mutations were present only in B-lymphoblasts (BCOR, NRAS) or myeloid cells (ASXL1, EZH2, RUNX1). These results indicate that both processes evolved from a common U2AF1-mutated precursor, which then acquired additional mutations during a process of divergent evolution and bilineal differentiation. Our findings highlight an atypical mechanism of BLL leukemogenesis and demonstrate the potential utility of fractionated sequencing in the characterization of acute leukemia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Trastornos Mieloproliferativos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Trastornos Mieloproliferativos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos