Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia

Michelle Churchman; Jonathan Low; Chunxu Qu; Elisabeth M Paietta; Lawryn Heath Kasper; Yunchao Chang; Debbie Payne-Turner; Mark J Althoff; Guangchun Song; Shann-Ching Chen; Jing Ma; Michael Rusch; Daniel J McGoldrick; Michael N Edmonson; Pankaj C Gupta; Yong-Dong Wang; William Caufield; Burgess B Freeman; John Carl Panetta; Sharyn D Baker; Yung-Li Yang; Kathryn G Roberts; Kelly McCastlain; Ilaria Iacobucci; Jennifer L Peters; Victoria E Centonze Frohlich; Faiyaz Notta; Stephanie M Dobson; Sasan Zandi; John Edgar Dick; Laura J Janke; Junmin Peng; Kiran Kumar Kodali; Vishwajeeth Reddy Pagala; Jaeki Min; Anand Mayasundari; Richard T Williams; Cheryl L Willman; Jacob M Rowe; Selina M Luger; Ross Alexander Dickins; Rodney Kiplin Guy; Taosheng Chen; Charles G Mullighan; Lie Li

doi:10.1016/j.ccell.2015.07.016

Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia

Michelle Churchman, Jonathan Low, Chunxu Qu, Elisabeth M Paietta, Lawryn Heath Kasper, Yunchao Chang, Debbie Payne-Turner, Mark J Althoff, Guangchun Song, Shann-Ching Chen, Jing Ma, Michael Rusch, Daniel J McGoldrick, Michael N Edmonson, Pankaj C Gupta, Yong-Dong Wang, William Caufield, Burgess B Freeman, John Carl Panetta, Sharyn D BakerYung-Li Yang, Kathryn G Roberts, Kelly McCastlain, Ilaria Iacobucci, Jennifer L Peters, Victoria E Centonze Frohlich, Faiyaz Notta, Stephanie M Dobson, Sasan Zandi, John Edgar Dick, Laura J Janke, Junmin Peng, Kiran Kumar Kodali, Vishwajeeth Reddy Pagala, Jaeki Min, Anand Mayasundari, Richard T Williams, Cheryl L Willman, Jacob M Rowe, Selina M Luger, Ross Alexander Dickins, Rodney Kiplin Guy, Taosheng Chen, Charles G Mullighan, Lie Li

Research output: Contribution to journal › Article › Research › peer-review

131 Citations (Scopus)

Abstract

Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

Original language	English
Pages (from-to)	343 - 356
Number of pages	14
Journal	Cancer Cell
Volume	28
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2015.07.016
Publication status	Published - 2015
Externally published	Yes

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Churchman, M., Low, J., Qu, C., Paietta, E. M., Kasper, L. H., Chang, Y., Payne-Turner, D., Althoff, M. J., Song, G., Chen, S-C., Ma, J., Rusch, M., McGoldrick, D. J., Edmonson, M. N., Gupta, P. C., Wang, Y-D., Caufield, W., Freeman, B. B., Panetta, J. C., ... Li, L. (2015). Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia. Cancer Cell, 28(3), 343 - 356. https://doi.org/10.1016/j.ccell.2015.07.016

@article{9e246418678640b08b6b609d2b96defd,

title = "Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia",

abstract = "Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.",

author = "Michelle Churchman and Jonathan Low and Chunxu Qu and Paietta, {Elisabeth M} and Kasper, {Lawryn Heath} and Yunchao Chang and Debbie Payne-Turner and Althoff, {Mark J} and Guangchun Song and Shann-Ching Chen and Jing Ma and Michael Rusch and McGoldrick, {Daniel J} and Edmonson, {Michael N} and Gupta, {Pankaj C} and Yong-Dong Wang and William Caufield and Freeman, {Burgess B} and Panetta, {John Carl} and Baker, {Sharyn D} and Yung-Li Yang and Roberts, {Kathryn G} and Kelly McCastlain and Ilaria Iacobucci and Peters, {Jennifer L} and {Centonze Frohlich}, {Victoria E} and Faiyaz Notta and Dobson, {Stephanie M} and Sasan Zandi and Dick, {John Edgar} and Janke, {Laura J} and Junmin Peng and Kodali, {Kiran Kumar} and Pagala, {Vishwajeeth Reddy} and Jaeki Min and Anand Mayasundari and Williams, {Richard T} and Willman, {Cheryl L} and Rowe, {Jacob M} and Luger, {Selina M} and Dickins, {Ross Alexander} and Guy, {Rodney Kiplin} and Taosheng Chen and Mullighan, {Charles G} and Lie Li",

year = "2015",

doi = "10.1016/j.ccell.2015.07.016",

language = "English",

volume = "28",

pages = "343 -- 356",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Elsevier",

number = "3",

}

Churchman, M, Low, J, Qu, C, Paietta, EM, Kasper, LH, Chang, Y, Payne-Turner, D, Althoff, MJ, Song, G, Chen, S-C, Ma, J, Rusch, M, McGoldrick, DJ, Edmonson, MN, Gupta, PC, Wang, Y-D, Caufield, W, Freeman, BB, Panetta, JC, Baker, SD, Yang, Y-L, Roberts, KG, McCastlain, K, Iacobucci, I, Peters, JL, Centonze Frohlich, VE, Notta, F, Dobson, SM, Zandi, S, Dick, JE, Janke, LJ, Peng, J, Kodali, KK, Pagala, VR, Min, J, Mayasundari, A, Williams, RT, Willman, CL, Rowe, JM, Luger, SM, Dickins, RA, Guy, RK, Chen, T, Mullighan, CG & Li, L 2015, 'Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia', Cancer Cell, vol. 28, no. 3, pp. 343 - 356. https://doi.org/10.1016/j.ccell.2015.07.016

TY - JOUR

T1 - Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia

AU - Churchman, Michelle

AU - Low, Jonathan

AU - Qu, Chunxu

AU - Paietta, Elisabeth M

AU - Kasper, Lawryn Heath

AU - Chang, Yunchao

AU - Payne-Turner, Debbie

AU - Althoff, Mark J

AU - Song, Guangchun

AU - Chen, Shann-Ching

AU - Ma, Jing

AU - Rusch, Michael

AU - McGoldrick, Daniel J

AU - Edmonson, Michael N

AU - Gupta, Pankaj C

AU - Wang, Yong-Dong

AU - Caufield, William

AU - Freeman, Burgess B

AU - Panetta, John Carl

AU - Baker, Sharyn D

AU - Yang, Yung-Li

AU - Roberts, Kathryn G

AU - McCastlain, Kelly

AU - Iacobucci, Ilaria

AU - Peters, Jennifer L

AU - Centonze Frohlich, Victoria E

AU - Notta, Faiyaz

AU - Dobson, Stephanie M

AU - Zandi, Sasan

AU - Dick, John Edgar

AU - Janke, Laura J

AU - Peng, Junmin

AU - Kodali, Kiran Kumar

AU - Pagala, Vishwajeeth Reddy

AU - Min, Jaeki

AU - Mayasundari, Anand

AU - Williams, Richard T

AU - Willman, Cheryl L

AU - Rowe, Jacob M

AU - Luger, Selina M

AU - Dickins, Ross Alexander

AU - Guy, Rodney Kiplin

AU - Chen, Taosheng

AU - Mullighan, Charles G

AU - Li, Lie

PY - 2015

Y1 - 2015

N2 - Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

AB - Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

UR - http://www.sciencedirect.com/science/article/pii/S1535610815002688

U2 - 10.1016/j.ccell.2015.07.016

DO - 10.1016/j.ccell.2015.07.016

M3 - Article

SN - 1535-6108

VL - 28

SP - 343

EP - 356

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia

Abstract

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