IL7R is associated with CNS infiltration and relapse in pediatric B-cell precursor acute lymphoblastic leukemia

Central nervous system (CNS) involvement in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is rarely detected at initial presentation. 1 Nevertheless, CNS relapse most frequently occurs in children who were initially diagnosed as CNS2 and did not have any high-risk characteristics. 2 Therefore, all patients receive intensive CNS-directed chemotherapy, 3 an approach associated with short- and long-term neurological toxicities. 4,5 The CNS microenvironment may contribute to chemoresistance and survival of leukemic cells. 6 Interleukin 15 (IL15) was shown to promote ALL survival in the hostile microenvironments of the CNS. 7,8 IL7 can be detected in the cerebrospinal fluid (CSF) and high levels have been associated with inflammatoryCNS disease, 9 which supports that IL7 may be produced by stromal cells in that niche upon different stimuli. 10 Also, elevated IL7 plasma levels were detected in BCP-ALL patients. 11 Here, we show that IL7R is highly expressed in pediatric BCP-ALL patients who were CNS+ at initial diagnosis, and that an upregulation of IL7R may predict CNS relapse. Using a xenograft model in immunodeficient mice, we show that IL7R is required for leukemic engraftment in vivo, and that targeting IL7R with monoclonal antibody reduces CNS leukemic infiltration.