Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells

Abstract

AbstractT‐cell acute lymphoblastic leukemia (T‐ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large‐scale screening of natural compound libraries to identify potential drugs against T‐ALL. We identified three low‐molecular‐weight compounds (auxarconjugatin‐B, rumbrin, and lavendamycin) that inhibited the proliferation of the T‐ALL cell line CCRF‐CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin‐B and rumbrin commonly contained a polyenyl 3‐chloropyrrol in their chemical structure, therefore we chose auxarconjugatin‐B for further analyses. Auxarconjugatin‐B suppressed the in vitro growth of five human T‐ALL cell lines and two T‐ALL patient‐derived cells, but not that of adult T‐cell leukemia patient‐derived cells. Cultured normal T cells were several‐fold resistant to auxarconjugatin‐B. Auxarconjugatin‐B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF‐CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti‐T‐ALL drugs.