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Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.
Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J.
Afiliación
  • Giustacchini A; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Thongjuea S; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Barkas N; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Woll PS; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Povinelli BJ; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Booth CAG; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Sopp P; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Norfo R; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Rodriguez-Meira A; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Ashley N; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Jamieson L; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Vyas P; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Anderson K; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Segerstolpe Å; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Qian H; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Olsson-Strömberg U; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Mustjoki S; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Sandberg R; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Jacobsen SEW; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Mead AJ; Haemopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Nat Med ; 23(6): 692-702, 2017 Jun.
Article en En | MEDLINE | ID: mdl-28504724
Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Leucemia Mielógena Crónica BCR-ABL Positiva / Crisis Blástica / Regulación Neoplásica de la Expresión Génica / Perfilación de la Expresión Génica / Análisis de la Célula Individual Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Leucemia Mielógena Crónica BCR-ABL Positiva / Crisis Blástica / Regulación Neoplásica de la Expresión Génica / Perfilación de la Expresión Génica / Análisis de la Célula Individual Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos