An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia
Menée initialement sur une cohorte de 14 patients pédiatriques atteints d'une leucémie aiguë mégacaryoblastique non associée à une trisomie 21, puis validée sur une cohorte complémentaire de 34 patients pédiatriques et 28 patients adultes, cette étude met en évidence une fusion des gènes CBFA2T3 et GLIS2 associée à une forme agressive de la maladie
To define the mutation spectrum in non-Down syndrome acute megakaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL samples. Our analysis identified a cryptic chromosome 16 inversion (inv(16)(p13.3q24.3)) in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.
º CBFA2T3-GLIS2 is a recurrent fusion gene in pediatric AMKL
º CBFA2T3-GLIS2 AMKL has a distinct expression profile and an inferior outcome
º CBFA2T3-GLIS2 induces BMP signaling and enhanced self-renewal of progenitor cells
Cancer cell , article en libre accès, 2011