Therapy-related acute myeloid leukemia with KMT2A-SNX9 gene fusion associated with a hyperdiploid karyotype after hemophagocytic lymphohistiocytosis

• Published in: Cancer genetics 2021-08, Vol.256-257, p.86-90
• Main Authors: Sardou-Cezar, Ingrid, Lopes, Bruno A., Andrade, Francianne Gomes, Fonseca, Teresa Cristina Cardoso, Fernandez, Teresa de Souza, Larghero, Patrizia, de Souza, Regiana Quinto, Loth, Gisele, Ribeiro, Lisandro Lima, Bonfim, Carmen, Morgado, Elissa Santos, Marschalek, Rolf, Meyer, Claus, Pombo-de-Oliveira, Maria S.
• Format: Article
• Language: English
• Subjects: Etoposide; Hemophagocytic lymphohistiocytosis; KMT2A-SNX9; MLL-r; Therapy-related acute myeloid leukemia
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2021.05.001

•Exposure to etoposide is strongly associated with therapy-related AML•KMT2A-SNX9 was identified in a t-AML with an abnormal karyotype using NGS method•HLH is a threatening disease, and its treatment should be handled carefully Therapy-related acute myeloid leukemia (t-AML) following treatment with topoisomerase-II inhibitors has been increasingly reported. These compounds (e.g. etoposide) promote DNA damage and are associated with KMT2A rearrangements. They are widely used as first-line treatment in hemophagocytic lymphohistiocytosis (HLH). Here we describe a newborn who developed t-AML after HLH treatment. We provide detailed clinical, cytogenetic, and molecular characteristics of this patient, including the identification of a novel gene fusion – KMT2A-SNX9 – in t-AML. Considering the dismal outcome of this case, we discuss the side-effects of etoposide administration during HLH treatment in infants.