Orbital Swelling: An Unusual Case of Relapsed Acute Lymphoblastic Leukaemia in A Preschool Child

Acute lymphoblastic leukaemia (ALL) is the most frequent childhood cancer. Children usually present with signs of bone marrow failure like recurrent or prolonged fever, pallor, lethargy, bleeding tendencies, bone pain and others. Occasionally they may present with sign of infiltration of leukaemic cells into other organs such as testicular and central nervous system, rarely to the periorbital or orbital region. Similarly in relapse cases, they typically presented either in bone marrow, central nervous system relapse or testicular but rarely orbital involvement. Here we report the clinical case of a five-year-old boy who developed relapsed B-ALL, presented to us with unilateral right eye swelling without other clinical findings and absence of blast cells in the peripheral blood film as well as bone marrow aspirate specimen.

The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13

B-cell acute lymphoblastic leukemia (B-ALL) occurs most commonly in children, while chronic myeloid leukemia (CML) is more frequent in adults. The myeloid bias of hematopoiesis in elderly individuals has been considered causative, but the age of the bone marrow (BM) microenvironment (BMM) may be contributory. Using various murine models of B-ALL in young versus old mice, we recapitulated B-ALL preponderance in children versus adults. We showed differential effects of young versus old BM macrophages on B-ALL cell function. Molecular profiling using RNA- and ATAC-seq revealed pronounced differences in young versus old BMM-derived macrophages and enrichment for gene sets associated with inflammation. In concordance with the role of C-X-C motif chemokine (CXCL) 13 for disease-associated B cell chemoattraction, we found CXCL13 to be highly expressed in young macrophages on a translational compared to a transcriptional level. Inhibition of CXCL13 in BM macrophages impaired leukemia cell migration and decreased the proliferation of cocultured B-ALL cells, while recombinant CXCL13 increased pAKT and B-ALL cell expansion. Pretreatment of B-ALL-initiating cells with CXCL13 accelerated B-ALL progression. Deficiency of Cxcr5, the receptor for CXCL13, on B-ALL-initiating cells prolonged murine survival, while high expression of CXCR5 in pediatric B-ALL may predict central nervous system relapse. CXCL13 staining was increased in bone sections from pediatric compared to adult B-ALL patients. Taken together, our study shows that the age of the BMM and, in particular, BM macrophages influence the leukemia phenotype. The CXCR5-CXCL13-axis may act as prognostic marker and an attractive novel target for the treatment of B-ALL.