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

Different driver mutations and/or chromosomal aberrations and dysregulated signaling between leukemia cells and the immune microenvironment have been implicated in the development of T-cell acute lymphoblastic leukemia (T-ALL). To better understand the 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) were profiled for 11 T-ALL patients (10 Dx, 5 paired EOI, 1 relapse) by single cell transcriptomics. T-ALL blasts were identified by comparison with healthy bone marrow cells. T-ALL blast-associated gene signature included SOX4, STMN1, CD99, HES4, and ARMH1 among the highest dysregulated genes, all of which together associated with poor prognosis in children with T-ALL (HR=2.7, LR P value=0.008)). The 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 hematopoetic 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. A total of 16 samples were collected from 11 T-ALL patients. 10 at diagnosis (Dx), 5 after therapy (EOI) and 1 at relapse. NOTE FROM SUBMITTER: raw data are not available due to patient privacy concerns.