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Letters to the Editor
granulocyte-macrophage colony-forming units,15 our results suggest that this also reflects the establishment of a program that can be induced by NA9 expression. The significant enrichment of H3K27ac marks in enhancers of genes of the GM-CSF signaling and inflammatory path- ways adds further support to this concept. In addition, we note that NA9 appears to induce many features of progression to BP disease but without accumulation of blasts, thus distinguishing it from results obtained in mouse models.4-6 Nevertheless, our findings strongly point to the NA9 signature identified here as one that is common to the BP populations that emerge spontaneous- ly in CML patients whose CP disease becomes uncon- trolled.
Ivan Sloma,1-3° Philip Beer,1 Christophe Desterke,4 Elizabeth Bulaeva,1 Misha Bilenky,5 Annaïck Carles,6 Michelle Moksa,6 Kamini Raghuram,1 Cedric Brimacombe,1 Karen Lambie,1 Ali G. Turhan,7 Orianne Wagner-Ballon,2,3 Philippe Gaulard,2,8 Keith Humphries,1 Martin Hirst5,6
and Connie J. Eaves1,9
1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; 2Université Paris Est Creteil, INSERM, IMRB, Creteil, France; 3Assistance Publique des Hôpitaux de Paris (AP-HP), Hopital Henri Mondor, Departement d’Hematologie et Immunologie, Creteil, France; 4Université Paris-Sud, Faculté de Médecine Kremlin Bicêtre, INSERM UMS 33 Villejuif, France; 5Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; 6Department of Microbiology and Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; 7Service d’Hématologie Biologique, Hôpital Universitaire Paris-Saclay, INSERM U935, AP-HP, Kremlin Bicêtre, France; 8INSERM UMRS955, Pathology Department, Hôpital Henri Mondor, AP-HP, Faculté de Médecine de Créteil, Université Paris-Est Créteil, Créteil, France and 9University of British Columbia, Department of Medical Genetics, Vancouver, British Columbia, Canada
°Present address: Université Paris Est Creteil, INSERM, IMRB and AP-HP, Hopital Henri Mondor, Departement d’Hematologie et Immunologie, Creteil, France
Correspondence: IVAN SLOMA - ivan.sloma@aphp.fr doi:10.3324/haematol.2020.249243
Disclosures: no conflicts of interest to disclose.
Contributions: IS and CJE designed the study. IS prepared the vectors with assistance from KR and CB. IS isolated the CD34+ cells, and with EB performed the transductions and with KR, CB and PB carried out the in vitro experiments. IS and PB performed the in vivo experiments and, with assistance from PG and OWB, the necropsy analyses. MH supervised the RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) studies. MM prepared the RNA-seq libraries. MB analyzed the primary RNA-seq data and differential expression. CD performed variant calling, in silico transcriptomics analysis and integration of RNA-seq and ChiP-seq data. IS and CD contributed to the tertiary RNA-seq analysis. MM
performed ChiP-seq experiments. AC did the primary and secondary analyses of ChiP-seq experiments while IS contributed to secondary and tertiary analyses. IS and CJE wrote the manuscript with input from PB, CD, MB and MM and approval from all authors.
Funding: IS received a grant from Cent pour Sang La Vie and AGT received a grant from the Oncostem program of the French national IPSC Infrastructure “Investissements d’Avenir” INGESTEM. CE received grants supported by funds from the Terry Fox Run and from CIHR. MH received grants supported by funds from the Terry Fox Run and the Terry Fox Research Institute (TFF-122869).
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