Cerebrospinal fluid attenuates the efficacy of methotrexate against acute lymphoblastic leukemia cells.

ABSTRACT: Treatment and prophylaxis of the central nervous system (CNS) is a standard component of acute lymphoblastic leukemia (ALL) therapy. However, CNS-directed therapies are a significant cause of morbidity, and CNS relapse remains a cause of treatment failure. CNS-directed ALL therapies must target leukemia cells within cerebrospinal fluid (CSF), a fluid that is compositionally distinct from plasma and has been shown to affect leukemia biology. Herein, we demonstrate that human CSF attenuates the potency and efficacy of antifolate drugs including methotrexate, the primary CNS-directed chemotherapeutic for >6 decades. Importantly, this effect of CSF on leukemia methotrexate sensitivity was reversible. Additional mechanistic studies support that diminished proliferation and activation of the int

SUBMITTER: Kang J 

PROVIDER: S-EPMC12082133 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature