The genetic basis and cell of origin of mixed phenotype acute leukaemia.

Autor: Alexander TB; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.; Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA., Gu Z; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Iacobucci I; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Dickerson K; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Choi JK; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Xu B; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Payne-Turner D; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Yoshihara H; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Loh ML; Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA., Horan J; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA., Buldini B; Department of Women and Child Health, Hemato-Oncology Division, University of Padova, Padova, Italy., Basso G; Department of Women and Child Health, Hemato-Oncology Division, University of Padova, Padova, Italy., Elitzur S; Pediatric Hematology-Oncology, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel., de Haas V; Prinses Maxima Centre, Utrecht, The Netherlands., Zwaan CM; Prinses Maxima Centre, Utrecht, The Netherlands.; Department of Pediatric Oncology, Erasmus MC-Sophia, Rotterdam, The Netherlands., Yeoh A; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Reinhardt D; Universitäts-Klinikum, Essen, Germany., Tomizawa D; Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan., Kiyokawa N; Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan., Lammens T; Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium., De Moerloose B; Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium., Catchpoole D; The Tumour Bank CCRU, The Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales, Australia., Hori H; Department of Pediatrics, Mie University, Tsu, Japan., Moorman A; Wolfson Childhood Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK., Moore AS; The University of Queensland Diamantina Institute & Children's Health, Brisbane, Queensland, Australia., Hrusak O; Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Meshinchi S; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA.; Children's Oncology Group, Arcadia, CA, USA., Orgel E; Children's Center for Cancer and Blood Disease, Children's Hospital Los Angeles, Los Angeles, CA, USA., Devidas M; University of Florida, Gainesville, FL, USA., Borowitz M; Johns Hopkins Medical Institutions, Baltimore, MD, USA., Wood B; University of Washington, Seattle, WA, USA., Heerema NA; The Ohio State University School of Medicine, Columbus, OH, USA., Carrol A; University of Alabama at Birmingham, Birmingham, AL, USA., Yang YL; Department of Laboratory Medicine and Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan., Smith MA; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA., Davidsen TM; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA., Hermida LC; Office of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., Gesuwan P; Office of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., Marra MA; Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada., Ma Y; Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada., Mungall AJ; Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada., Moore RA; Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada., Jones SJM; Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada., Valentine M; Cytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN, USA., Janke LJ; 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., Pui CH; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ding L; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Zhang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Nichols KE; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Downing JR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Cao X; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Shi L; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Pounds S; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Newman S; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Pei D; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Guidry Auvil JM; Office of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., Gerhard DS; Office of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., Hunger SP; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Inaba H; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. hiroto.inaba@stjude.org., Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. charles.mullighan@stjude.org.
Jazyk: angličtina
Zdroj: Nature [Nature] 2018 Oct; Vol. 562 (7727), pp. 373-379. Date of Electronic Publication: 2018 Sep 12.
DOI: 10.1038/s41586-018-0436-0
Abstrakt: Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.
Databáze: MEDLINE