| Literature DB >> 29681510 |
Michelle L Churchman1, Maoxiang Qian2, Geertruy Te Kronnie3, Ranran Zhang4, Wenjian Yang2, Hui Zhang5, Tobia Lana3, Paige Tedrick6, Rebekah Baskin6, Katherine Verbist6, Jennifer L Peters7, Meenakshi Devidas8, Eric Larsen9, Ian M Moore1, Zhaohui Gu1, Chunxu Qu1, Hiroki Yoshihara1, Shaina N Porter10, Shondra M Pruett-Miller10, Gang Wu11, Elizabeth Raetz12, Paul L Martin13, W Paul Bowman14, Naomi Winick15, Elaine Mardis16, Robert Fulton17, Martin Stanulla18, William E Evans19, Mary V Relling19, Ching-Hon Pui20, Stephen P Hunger21, Mignon L Loh22, Rupert Handgretinger23, Kim E Nichols20, Jun J Yang24, Charles G Mullighan25.
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.Entities:
Keywords: ALL; IKAROS; IKZF1; acute lymphoblastic leukemia; drug response; familial leukemia; germline genetic variation; immunodeficiency; predisposition
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Year: 2018 PMID： 29681510 PMCID： PMC5953820 DOI： 10.1016/j.ccell.2018.03.021
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743