Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia

被引：154

作者：

Churchman, Michelle L. ^{[1
]}

Qian, Maoxiang ^{[2
]}

te Kronnie, Geertruy ^{[3
]}

Zhang, Ranran ^{[4
]}

Yang, Wenjian ^{[2
]}

Zhang, Hui ^{[2
,4
]}

Lana, Tobia ^{[3
]}

Tedrick, Paige ^{[5
]}

Baskin, Rebekah ^{[5
]}

Verbist, Katherine ^{[5
]}

Peters, Jennifer L. ^{[6
]}

Devidas, Meenakshi ^{[7
]}

Larsen, Eric ^{[8
]}

Moore, Ian M. ^{[1
]}

Gu, Zhaohui ^{[1
]}

Qu, Chunxu ^{[1
]}

Yoshihara, Hiroki ^{[1
]}

Porter, Shaina N. ^{[9
]}

Pruett-Miller, Shondra M. ^{[9
]}

Wu, Gang ^{[10
]}

Raetz, Elizabeth ^{[11
]}

Martin, Paul L. ^{[12
]}

Bowman, W. Paul ^{[13
]}

Winick, Naomi ^{[14
]}

Mardis, Elaine ^{[15
]}

Fulton, Robert ^{[16
]}

Stanulla, Martin ^{[17
]}

Evans, William E. ^{[2
,18
]}

Relling, Mary V. ^{[2
,18
]}

Pui, Ching-Hon ^{[5
,18
]}

Hunger, Stephen P. ^{[19
,20
,21
]}

Loh, Mignon L. ^{[22
,23
]}

Handgretinger, Rupert ^{[24
]}

Nichols, Kim E. ^{[5
,18
]}

Yang, Jun J. ^{[2
,5
,18
]}

Mullighan, Charles G. ^{[1
,18
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA

[3] Univ Padua, Dept Womens & Childrens Hlth, I-35128 Padua, Italy

[4] Guangzhou Med Univ, Affiliated Hosp 1, Dept Pediat, Guangzhou 510120, Guangdong, Peoples R China

[5] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[6] St Jude Childrens Res Hosp, Cellular Imaging Shared Resource, Memphis, TN 38105 USA

[7] Univ Florida, Coll Med, Dept Biostat Epidemiol & Hlth Policy Res, Gainesville, FL 32610 USA

[8] Maine Childrens Canc Program, Scarborough, ME 04074 USA

[9] St Jude Childrens Res Hosp, Ctr Adv Genome Engn, Memphis, TN 38105 USA

[10] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA

[11] NYU, Div Pediat Hematol Oncol, New York, NY 10016 USA

[12] Duke Univ, Dept Pediat, Durham, NC 27708 USA

[13] Cook Childrens Med Ctr, Ft Worth, TX 76104 USA

[14] Univ Texas Southwestern Med Ctr Dallas, Pediat Hematol Oncol, Dallas, TX 75390 USA

[15] Nationwide Childrens Hosp, Inst Genom Med, Columbus, OH 43205 USA

[16] Washington Univ, McDonnell Genome Inst, Sch Med, St Louis, MO 63108 USA

[17] Hannover Med Sch, Pediat Hematol & Oncol, D-30625 Hannover, Germany

[18] St Jude Childrens Res Hosp, Hematol Malignancies Program, Memphis, TN 38105 USA

[19] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA

[20] Univ Penn, Ctr Childhood Canc Res, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[21] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[22] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94158 USA

[23] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA

[24] Childrens Univ Hosp, Dept Hematol Oncol, D-72076 Tubingen, Germany

来源：

CANCER CELL | 2018年 / 33卷 / 05期

关键词：

GENOME-WIDE ASSOCIATION; TOTAL THERAPY; B-CELLS; IKAROS; RISK; ETV6; SUSCEPTIBILITY; MUTATIONS; VARIANTS; THROMBOCYTOPENIA;

D O I：

10.1016/j.ccell.2018.03.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：937 / +

页数：20

共 63 条

[1]

Adzhubei Ivan, 2013, Curr Protoc Hum Genet, VChapter 7, DOI 10.1002/0471142905.hg0720s76

[2] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[3] Inherited susceptibility to pre B-ALL caused by germline transmission of PAX5 c. 547G>A [J].

Auer, F. ;

Rueschendorf, F. ;

Gombert, M. ;

Husemann, P. ;

Ginzel, S. ;

Izraeli, S. ;

Harit, M. ;

Weintraub, M. ;

Weinstein, O. Y. ;

Lerer, I. ;

Stepensky, P. ;

Borkhardt, A. ;

Hauer, J. .

LEUKEMIA, 2014, 28 (05) :1136-1138

[4] Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia [J].

Boulos, Nidal ;

Mulder, Heather L. ;

Calabrese, Christopher R. ;

Morrison, Jeffrey B. ;

Rehg, Jerold E. ;

Relling, Mary V. ;

Sherr, Charles J. ;

Williams, Richard T. .

BLOOD, 2011, 117 (13) :3585-3595

[5] Augmented Therapy Improves Outcome for Pediatric High Risk Acute Lymphocytic Leukemia: Results Of Children's Oncology Group Trial P9906 [J].

Bowman, W. Paul ;

Larsen, Eric L. ;

Devidas, Meenakshi ;

Linda, Stephen B. ;

Blach, Laurie ;

Carroll, Andrew J. ;

Carroll, William L. ;

Pullen, D. Jeanette ;

Shuster, Jonathan ;

Willman, Cheryl L. ;

Winick, Naomi ;

Camitta, Bruce M. ;

Hunger, Stephen P. ;

Borowitz, Michael J. .

PEDIATRIC BLOOD & CANCER, 2011, 57 (04) :569-577

[6] CONSERTING: integrating copy-number analysis with structural-variation detection [J].

Chen, Xiang ;

Gupta, Pankaj ;

Wang, Jianmin ;

Nakitandwe, Joy ;

Roberts, Kathryn ;

Dalton, James D. ;

Parker, Matthew ;

Patel, Samir ;

Holmfeldt, Linda ;

Payne, Debbie ;

Easton, John ;

Ma, Jing ;

Rusch, Michael ;

Wu, Gang ;

Patel, Aman ;

Baker, Suzanne J. ;

Dyer, Michael A. ;

Shurtleff, Sheila ;

Espy, Stephen ;

Pounds, Stanley ;

Downing, James R. ;

Ellison, David W. ;

Mullighan, Charles G. ;

Zhang, Jinghui .

NATURE METHODS, 2015, 12 (06) :527-+

[7] Synergism of FAK and tyrosine kinase inhibition in Ph+ B-ALL [J].

Churchman, Michelle L. ;

Evans, Kathryn ;

Richmond, Jennifer ;

Robbins, Alissa ;

Jones, Luke ;

Shapiro, Irina M. ;

Pachter, Jonathan A. ;

Weaver, David T. ;

Houghton, Peter J. ;

Smith, Malcolm A. ;

Lock, Richard B. ;

Mullighan, Charles G. .

JCI INSIGHT, 2016, 1 (04)

[8] Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia [J].

Churchman, Michelle L. ;

Low, Jonathan ;

Qu, Chunxu ;

Paietta, Elisabeth M. ;

Kasper, Lawryn H. ;

Chang, Yunchao ;

Payne-Turner, Debbie ;

Althoff, Mark J. ;

Song, Guangchun ;

Chen, Shann-Ching ;

Ma, Jing ;

Rusch, Michael ;

McGoldrick, Dan ;

Edmonson, Michael ;

Gupta, Pankaj ;

Wang, Yong-Dong ;

Caufield, William ;

Freeman, Burgess ;

Li, Lie ;

Panetta, John C. ;

Baker, Sharyn ;

Yang, Yung-Li ;

Roberts, Kathryn G. ;

McCastlain, Kelly ;

Iacobucci, Ilaria ;

Peters, Jennifer L. ;

Centonze, Victoria E. ;

Notta, Faiyaz ;

Dobson, Stephanie M. ;

Zandi, Sasan ;

Dick, John E. ;

Janke, Laura ;

Peng, Junmin ;

Kodali, Kiran ;

Pagela, Vishwajeeth ;

Min, Jaeki ;

Mayasundari, Anand ;

Williams, Richard T. ;

Willman, Cheryl L. ;

Rowe, Jacob ;

Luger, Selina ;

Dickins, Ross A. ;

Guy, R. Kiplin ;

Chen, Taosheng ;

Mullighan, Charles G. .

CANCER CELL, 2015, 28 (03) :343-356

[9] Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding [J].

Cobb, BS ;

Morales-Alcelay, S ;

Kleiger, G ;

Brown, KE ;

Fisher, AG ;

Smale, ST .

GENES & DEVELOPMENT, 2000, 14 (17) :2146-2160

[10] A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study [J].

Den Boer, Monique L. ;

van Slegtenhorst, Marjon ;

De Menezes, Renee X. ;

Cheok, Meyling H. ;

Buijs-Gladdines, Jessica G. C. A. M. ;

Peters, Susan T. C. J. M. ;

Van Zutven, Laura C. M. ;

Beverloo, H. Berna ;

Van der Spek, Peter J. ;

Escherich, Gaby ;

Horstmann, Martin A. ;

Janka-Schoub, Gritta E. ;

Kamps, Willem A. ;

Evans, William E. ;

Pieters, Rob .

LANCET ONCOLOGY, 2009, 10 (02) :125-134

← 1 2 3 4 5 6 7 →