Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia

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 adhes...

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Vydáno v:	Cancer cell Ročník 33; číslo 5; s. 937
Hlavní autoři:	Churchman, Michelle L, Qian, Maoxiang, Te Kronnie, Geertruy, Zhang, Ranran, Yang, Wenjian, Zhang, Hui, Lana, Tobia, Tedrick, Paige, Baskin, Rebekah, Verbist, Katherine, Peters, Jennifer L, Devidas, Meenakshi, Larsen, Eric, Moore, Ian M, Gu, Zhaohui, Qu, Chunxu, Yoshihara, Hiroki, Porter, Shaina N, Pruett-Miller, Shondra M, Wu, Gang, Raetz, Elizabeth, Martin, Paul L, Bowman, W Paul, Winick, Naomi, Mardis, Elaine, Fulton, Robert, Stanulla, Martin, Evans, William E, Relling, Mary V, Pui, Ching-Hon, Hunger, Stephen P, Loh, Mignon L, Handgretinger, Rupert, Nichols, Kim E, Yang, Jun J, Mullighan, Charles G
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 14.05.2018
Témata:	Animals Child Female Frameshift Mutation Genetic Predisposition to Disease Germ-Line Mutation Humans Ikaros Transcription Factor - genetics Ikaros Transcription Factor - metabolism Male Mice Neoplasm Transplantation Pedigree Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Sequence Analysis, DNA drug response ALL germline genetic variation acute lymphoblastic leukemia IKAROS predisposition immunodeficiency IKZF1 familial leukemia
ISSN:	1878-3686, 1878-3686
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1878-3686 1878-3686
DOI:	10.1016/j.ccell.2018.03.021