Abstract:
:Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Churchman ML,Qian M,Te Kronnie G,Zhang R,Yang W,Zhang H,Lana T,Tedrick P,Baskin R,Verbist K,Peters JL,Devidas M,Larsen E,Moore IM,Gu Z,Qu C,Yoshihara H,Porter SN,Pruett-Miller SM,Wu G,Raetz E,Martin PL,Bowmandoi
10.1016/j.ccell.2018.03.021subject
Has Abstractpub_date
2018-05-14 00:00:00pages
937-948.e8issue
5eissn
1535-6108issn
1878-3686pii
S1535-6108(18)30126-0journal_volume
33pub_type
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