Pediatrics & Therapeutics
Open Access

Abstract

Fighting against the CNS Invasion of Pediatric Leukemia

Seiji Fukuda

One of the major complications that negatively influence prognoses in leukemia patients is extramedullary infiltration or dissemination of leukemia cells, in particular, infiltration into the central nervous system (CNS). For instance, CNS relapses are common in patients with childhood T-ALL . However, intensified intrathecal chemotherapy and cranial irradiation as prophylaxis of CNS relapse can lead to serious adverse side effects, particularly secondary tumors, bone marrow suppression, growth impairment and endocrine complications , indicating that more selective therapeutic strategies are warranted. Leukemia cells are believed to emerge in the bone marrow from hematopoietic stem progenitor cells as a consequence of accumulation of oncogenic mutations. They subsequently move into the blood circulation and home to other organs or different sites within the marrow. Leukemia cells occupy normal hematopoietic niches and impair the production of functionally normal blood cells, demonstrating that the dissemination of acute leukemia cells is a crucial step in leukemic progression. However, the current chemotherapies and specific molecule-targeting drugs were designed to kill leukemia cells, but none of them is able to antagonize leukemia cell movement and trafficking. Blocking leukemia cell invasion and migration may represent a rational alternative strategy to minimize treatment-associated mortality and serious adverse effects.