Acute Myeloid Leukemia, hemophagocytosis and EBV susceptibility in a patient with PI3KR5 mutation

MURRAY C.; STODDART, J.; RODRIGUEZ BROGGI M.G.; DE MARTINO, MARA; ZWIRNER, NORBERTO WALTER; CABANA, J.; ROSENZWEIG, SERGIO; CALDIROLA, MARÍA SOLEDAD; BEZRODNIK, LILIANA; TORRES, NICOLÁS IGNACIO; URIARTE, IGNACIO; BERNASCONI, ANDREA; NIEMELA, J.; GAILLARD, MARÍA ISABEL; SCHILLACI, ROXANA

Barcelona

Congreso; 17th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2016); 2016

European Society for Immunodeficiencies

Primaryimmune deficiencies (PIDs) are commonly characterized by an increasedsusceptibility to specific infections and, in certain instances, a higherincidence of malignancies. Here we present a case of a boy with unusualassociation of acute mielocitic leukemia (AML), Haemophagositosis syndrome(HLH), lymphomatoid granulomatosis and disseminated CMV and EBV susceptibility.First of 4boys born from healthy non consanguineous parents, healthy until the age of 12years when he presented first episode of M3 AML and  2 episodes of HLH that resolved with HLH 2004protocol treatment. Ten months later he presented EBV-related lymphomatoidgranulomatosis affecting his lungs and skin followed by disseminated CMVinfection. Immuneevaluation detected severe hipogammaglobulinemia, AND lymphopenia, withextremely low counts of B cells, NK cells and iNKT cells. T cells showedCD4/CD8 inversion, with the CD8+ T cell compartment skewed to terminal effectorphenotype (CD57). Expression of citoplasmatic SAP and XIAP was normal as wasCD107 degranulation and perforin expression. A rareheterozygous substitution in PIK3R5 gene (c.523G>A p.V175M) was detected bytargeted NGS and confirmed by Sanger sequencing. Functional assays revealedabsent Akt phosphorilation in the patient?s cells, both at baseline and afterstimulation. Therefore,here we report a patient with heterozygous PIK3R5 V175M mutation, abnormal PI3K signaling, combinedimmunodeficiency phenotype affecting T, B, NK and iNKT cells, which wasassociated with increased susceptibility to AML, HLH and severe/disseminatedviral infections.