title: High proportions of CD4⁺ T cells among residual bone marrow T cells in childhood acute lymphoblastic leukemia are associated with favorable early responses.
abstract: Residual nonmalignant T cells in the bone marrow of patients with acute leukemias may be involved in active immune responses to leukemic cells. Here, we investigated the phenotypic signature of T cells present at diagnosis in 39 pediatric patients with acute lymphoblastic leukemia (ALL) treated within standardized ALL-BFM study protocols. Previously described age associations of lymphocyte subpopulations in the peripheral blood of healthy children were reproduced in leukemic bone marrow. Analysis of individual lymphocyte parameters and risk-associated variables using univariate linear regression models revealed a correlation of higher CD4/CD8 ratios at diagnosis with a favorable bone marrow response on day 15. Separate analysis of CD4⁺ cells with the CD4⁺CD25(hi)FoxP3⁺ T(reg) cell phenotype showed that the association was caused by non-T(reg) CD4⁺ cells. The association of higher CD4/CD8 ratios with a favorable bone marrow response on day 15 of treatment persisted in a cohort extended to 69 patients. We conclude that CD4⁺ non-T(reg) cells in leukemic bone marrow at diagnosis may have a role in early response to treatment. Prospective analysis of the CD4/CD8 ratio in a large cohort of pediatric patients is now needed. Moreover, future experiments will establish the functional role of the individual T cell subsets in immune control in pediatric ALL.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Lustfeld
authors.forename: Bianca
authors.initials: B
authors.lastname: Altvater
authors.forename: Martina
authors.initials: M
authors.lastname: Ahlmann
authors.forename: Sandra
authors.initials: S
authors.lastname: Ligges
authors.forename: Peter
authors.initials: P
authors.lastname: Brinkrolf
authors.forename: Annegret
authors.initials: A
authors.lastname: Rosemann
authors.forename: Anja
authors.initials: A
authors.lastname: Moericke
authors.forename: Claudia
authors.initials: C
authors.lastname: Rossig
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D016516:CD4-CD8 Ratio; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*