Gruber, T.A., Larson Gedman, A., Zhang, J., Koss, C.S., Marada, S., Ta, H.Q., Chen, S.C., Su, X., Ogden, S.K., Dang, J., Wu, G., Gupta, V., Andersson, A.K., Pounds, S., Shi, L., Easton, J., Barbato, M.I., Mulder, H.L., Manne, J., Wang, J., Rusch, M., Ranade, S., Ganti, R., Parker, M., Ma, J., Radtke, I., Ding, L., Cazzaniga, G., Biondi, A., Kornblau, S.M., Ravandi, F., Kantarjian, H., Nimer, S.D., Döhner, K., Döhner, H., Ley, T.J., Ballerini, P., Shurtleff, S., Tomizawa, D., Adachi, S., Hayashi, Y., Tawa, A., Shih, L.Y., Liang, D.C., Rubnitz, J.E., Pui, C.H., Mardis, E.R., Wilson, R.K., Downing, J.R. (2012). An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.  Cancer Cell 22(5): 683--697.

FBrf0263059

Research paper

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.

PMC3547667 (PMC) (EuropePMC)