Daniel Birnbaum’s group contributes to a study revisiting the classification of Acute ErythroLeukemia (AEL, also known as AML-M6), a rare but aggressive hematologic malignancy. The study characterized the molecular alterations of 33 AEL samples as well as their transcriptomic profiles, revealing that AEL is a molecularly heterogeneous disease and more than 25% of AEL patients showed aberrant expression of key transcriptional regulators. Functional assays were performed by ectopic expression of these factors in murine erythroid progenitors, which led to blocked in vitro erythroid differentiation and to cell immortalization. These data indicate that the erythroid identity of AEL results in part from the aberrant activity of key erythroid transcription factors during hematopoiesis.
Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers.
Fagnan A, Bagger FO, Piqué-Borràs MR, Ignacimouttou C, Caulier A, Lopez C, Robert E, Uzan B, Gelsi-Boyer V, Aid Z, Thirant C, Moll U, Tauchmann S, Kurtovic-Kozaric A, Maciejewski JP, Dierks C, Spinelli O, Salmoiraghi S, Pabst T, Shimoda K, Deleuze V, Lapillonne H, Sweeney C, Mansat-De Mas V, Leite B, Kadri Z, Malinge S, de Botton S, Micol JB, Kile BT, Carmichael CL, Iacobucci I, Mullighan CG, Carroll MP, Valent P, Bernard OA, Delabesse E, Vyas P, Birnbaum D, Anguita E, Garcon L, Soler E, Schwaller J, Mercher T.
Blood. 2020 Apr 29. pii: blood.2019003062.