RESUMEN
An 11-month-old female presented to the emergency department with a 2-week history of fever, increasing fussiness, emesis, and decreased urine output. She was diagnosed with acute myelogenous leukemia. Systemic chemotherapy with intensified intrathecal cytarabine was started, and the patient achieved a clinical remission after the first course of induction. Towards the end of her second course of induction she developed pseudohypopyon in each eye on consecutive days, heralding a central nervous system relapse.
Asunto(s)
Cámara Anterior/patología , Oftalmopatías/diagnóstico , Leucemia Mielomonocítica Aguda/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Femenino , Humanos , Lactante , Inyecciones Espinales , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/terapia , Pronóstico , Supuración/diagnósticoRESUMEN
Cancer cells acquire disruptions in normal signal transduction pathways and homeostatic mechanisms that would trigger apoptosis in normal cells. These abnormalities include genomic instability, oncogene activation, and growth factor independent proliferation. Therefore, cancer cells likely require a block in apoptosis in order to survive. Overexpression of the antiapoptotic protein BCL-2 provides a block in apoptosis that is frequently observed in cancer cells. We have developed methods for the detection and analysis of BCL-2 dependence and here apply them to acute lymphoblastic leukemia (ALL). BH3 profiling, a mitochondrial assay that classifies blocks in the intrinsic apoptotic pathway, indicated a dependence on BCL-2 of both ALL cell lines and primary samples. This dependence predicted that BCL-2 would be complexed with select pro-death BH3 family proteins, a prediction confirmed by the isolation of BCL-2 complexes with BIM. Furthermore, the BH3 profiling and protein analysis predicted that ALL cell lines and primary cells would be sensitive to ABT-737 as a single agent. Finally, BH3 profiling and protein studies accurately predicted a relative degree of sensitivity to BCL-2 antagonism in cell lines. The ALL cells studied exhibit BCL-2 dependence, supporting clinical trials of BCL-2 antagonists in ALL as single agents or combination therapies.