Mapping the cellular origin and early evolution of leukemia in Down syndrome-Reference-Cited by-同舟云学术

Mapping the cellular origin and early evolution of leukemia in Down syndrome

Published:2021-07-09 Issue:6551 Volume:373 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wagenblast Elvin¹^ORCID,Araújo Joana¹²³⁴⁵,Gan Olga I.¹,Cutting Sarah K.¹,Murison Alex¹,Krivdova Gabriela¹⁶,Azkanaz Maria¹,McLeod Jessica L.¹,Smith Sabrina A.¹⁶,Gratton Blaise A.¹^ORCID,Marhon Sajid A.¹^ORCID,Gabra Martino⁷^ORCID,Medeiros Jessie J. F.¹⁶⁸^ORCID,Manteghi Sanaz⁹^ORCID,Chen Jian⁹,Chan-Seng-Yue Michelle¹⁸^ORCID,Garcia-Prat Laura¹^ORCID,Salmena Leonardo¹⁷^ORCID,De Carvalho Daniel D.¹¹⁰^ORCID,Abelson Sagi⁶⁸^ORCID,Abdelhaleem Mohamed¹¹^ORCID,Chong Karen¹²¹³,Roifman Maian¹²¹³,Shannon Patrick¹⁴,Wang Jean C. Y.¹¹⁵¹⁶^ORCID,Hitzler Johann K.⁹¹⁷¹⁸^ORCID,Chitayat David¹²¹³,Dick John E.¹⁶^ORCID,Lechman Eric R.¹^ORCID

Affiliation:

1. Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

2. Department of Hematology, Centro Hospitalar Universitário de São João, Porto, 4200-319, Portugal.

3. Faculty of Medicine, University of Porto, Porto, 4200-319, Portugal.

4. Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, 4200-135, Portugal.

5. Instituto Nacional de Investigação Biomédica, University of Porto, Porto, 4200-135, Portugal.

6. Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

7. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.

8. Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

9. Program in Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 1X8, Canada.

10. Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.

11. Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

12. The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON M5S 1A8, Canada.

13. Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON M5S 1A8, Canada.

14. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON M5S 1A8, Canada.

15. Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

16. Division of Medical Oncology and Hematology, University Health Network, Toronto, Ontario M5G 2M9, Canada.

17. Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.

18. Division of Hematology and Oncology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Abstract

Down with leukemia Down syndrome is a congenital disorder caused by the trisomy of chromosome 21, and it is associated with a greatly increased risk of leukemia with origins in fetal development. Infants with Down syndrome are often born with a preleukemic condition, which later resolves in most cases. By using gene-edited human cells implanted into mouse models, Wagenblast et al. recapitulated the development of preleukemia and leukemia in the context of Down syndrome (see the Perspective by Roberts and Vyas). A specific mutation triggered a preleukemic condition in the context of trisomy 21 as expected, but progression to full-blown leukemia required a different genetic path and was not dependent on trisomy 21. Science , abf6202, this issue p. eabf6202 ; see also abj3957, p. 155

Funder

Alex’s Lemonade Stand Foundation for Childhood Cancer

Leukemia and Lymphoma Society

Ontario Institute for Cancer Research

International Development Research Centre

Canadian Cancer Society

Human Frontier Science Program

Portuguese Foundation for Science and Technology

Canada Research Chairs

Canadian Institutes for Health Research

Princess Margaret Cancer Centre Foundation

Terry Fox Research Institute Program Project Grant