Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis

• Authors: Swati S Bhasin, Emory University; Beena E Thomas, Emory University; Ryan Summers, Emory University; Debasree Sarkar, Emory University; Hope Mumme, Emory University; William Pilcher, Georgia Institute of Technology; Mohamed Emam, Emory University; Sunil S Raikar, Emory University; Sunita I Park, Emory University; Sharon M Castellino, Emory University; Douglas K Graham, Emory University; Manoj Bhasin, Emory University; Deborah DeRyckere, Emory University
• Journal Title: SCIENTIFIC REPORTS
• Volume: Volume 13, Number 1
• Publisher: NATURE PORTFOLIO | 2023-08-02, Pages 12556-12556
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41598-023-39152-z
• Subjects: Health Sciences, Oncology; Engineering, Biomedical; Health Sciences, Pathology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; CANCER; MUTATIONS; SURVIVAL; PROLIFERATION; INHIBITION; EXPRESSION; PROTEINS; RELAPSE; TARGET; SOX4

Abstract

Different driver mutations and/or chromosomal aberrations and dysregulated signaling interactions between leukemia cells and the immune microenvironment have been implicated in the development of T-cell acute lymphoblastic leukemia (T-ALL). To better understand changes in the bone marrow microenvironment and signaling pathways in pediatric T-ALL, bone marrows collected at diagnosis (Dx) and end of induction therapy (EOI) from 11 patients at a single center were profiled by single cell transcriptomics (10 Dx, 5 paired EOI, 1 relapse). T-ALL blasts were identified by comparison with healthy bone marrow cells. T-ALL blast-associated gene signature included SOX4, STMN1, JUN, HES4, CDK6, ARMH1 among the most significantly overexpressed genes, some of which are associated with poor prognosis in children with T-ALL. Transcriptome profiles of the blast cells exhibited significant inter-patient heterogeneity. Post induction therapy expression profiles of the immune cells revealed significant changes. Residual blast cells in MRD+ EOI samples exhibited significant upregulation (P < 0.01) of PD-1 and RhoGDI signaling pathways. Differences in cellular communication were noted in the presence of residual disease in T cell and hematopoietic stem cell compartments in the bone marrow. Together, these studies generate new insights and expand our understanding of the bone marrow landscape in pediatric T-ALL.