An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.

Abstract:

: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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Gruber TA,Larson Gedman A,Zhang J,Koss CS,Marada S,Ta HQ,Chen SC,Su X,Ogden SK,Dang J,Wu G,Gupta V,Andersson AK,Pounds S,Shi L,Easton J,Barbato MI,Mulder HL,Manne J,Wang J,Rusch M,Ranade S,Ganti R,Parker M,

doi

10.1016/j.ccr.2012.10.007

subject

Has Abstract

pub_date

2012-11-13 00:00:00

pages

683-97

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(12)00438-2

journal_volume

22

pub_type

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