Establishment of a t(11;19), KMT2A Rearranged B-ALL Cell Line for Preclinical Evaluation and Novel Therapeutics Development for Refractory Infant Leukemia

Le résumé fourni par la source

Leukemia, diagnosed in children less than 12 months of age, is a rare condition with an aggressive disease presentation and poor response to conventional chemotherapeutic agents. In addition, the unique vulnerability of the affected population does not always permit the use of markedly intense regimens with higher doses of cytotoxic agents. However, the unique biology of these leukemic cells also provides opportunities for the identification of effective and potentially well-tolerated targeted therapeutic strategies. In this report, we describe the establishment and characterization of a cell line from the blasts of an infant diagnosed with refractory B-cell acute lymphoblastic leukemia (ALL) carrying the characteristic histone lysine methyltransferase 2A (KMT2A) gene rearrangement. This cell line consists of rapidly proliferating clones of cells with chemosensitivity patterns previously described for KMT2A rearranged leukemia cells, including relative resistance to glucocorticoids and sensitivity to cytarabine. We also show effective targetability with menin inhibitors, indicating the activity of abnormal KMT2A-related pathways and the potential utility of this cell line in comprehensive drug library screens. Overall, our findings report the establishment and in vitro validation of a cell line for research into key aspects of infant leukemia biology and targeted therapeutics development.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.