Inactivation of the Cdkn2a locus cooperates with HMGA1 to drive T-cell leukemogenesis

被引：19

作者：

Di Cello, Francescopaolo ^{[1
,2
]}

Dhara, Surajit ^{[1
,2
]}

Hristov, Alexandra C. ^{[3
]}

Kowalski, Jeanne ^{[4
,5
]}

Elbahloul, Ossama ^{[1
,2
,6
]}

Hillion, Joelle ^{[1
,2
]}

Roy, Sujayita ^{[1
,2
]}

Meijerink, Jules P. P. ^{[8
]}

Winter, Stuart S. ^{[9
]}

Larson, Richard S. ^{[10
]}

Huso, David L. ^{[3
,5
,7
]}

Resar, Linda ^{[1
,2
,5
,6
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Div Hematol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA

[8] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands

[9] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA

[10] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA

来源：

LEUKEMIA & LYMPHOMA | 2013年 / 54卷 / 08期

关键词：

T-cell acute leukemia; HMGA1; mouse models; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION; TRANSGENIC MICE; STEM-CELL; UTERINE TUMORIGENESIS; TUMOR SUPPRESSION; LUNG-CANCER; TARGET; I/Y;

D O I：

10.3109/10428194.2013.764422

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia with high relapse rates compared to B-lineage ALL. We previously showed that HMGA1a transgenic mice develop aggressive T-ALL, indicating that HMGA1 causes leukemic transformation in vivo. HMGA1 is also highly expressed in embryonic stem cells, hematopoietic stem cells and diverse, refractory human cancers. Disruption of the CDKN2A tumor suppressor locus occurs in most cases of T-ALL and is thought to contribute to leukemic transformation. To determine whether loss of function of CDKN2A cooperates with HMGA1 in T-ALL, we crossed HMGA1a transgenics onto a Cdkn2a null background. We discovered that T-ALL is markedly accelerated in HMGA1a transgenic Cdkn2a null mice. In addition, these mice recapitulate salient clinical and pathologic features of human T-ALL. HMGA1 is also highly overexpressed in human T-ALL. These findings suggest that HMGA1 plays a causative role in T-ALL and could represent a rational therapeutic target.

引用

页码：1762 / 1768

页数：7

共 52 条

[11] HMGA2 participates in transformation in human lung cancer [J].

Di Cello, Francescopaolo ;

Hillion, Joelle ;

Hristov, Alexandra ;

Wood, Lisa J. ;

Mukherjee, Mita ;

Schuldenfrei, Andrew ;

Kowalski, Jeanne ;

Bhattacharya, Raka ;

Ashfaq, Raheela ;

Resar, Linda M. S. .

MOLECULAR CANCER RESEARCH, 2008, 6 (05) :743-750

[12] HMG-I/Y in human breast cancer cell lines [J].

Dolde, CE ;

Mukherjee, M ;

Cho, C ;

Resar, LMS .

BREAST CANCER RESEARCH AND TREATMENT, 2002, 71 (03) :181-191

[13] RETRACTED: Haploinsufficiency of the Hmga1 gene causes cardiac hypertrophy and myelo-lymphoproliferative disorders in mice (Retracted article. See vol. 78, pg. 6908, 2018) [J].

Fedele, M ;

Fidanza, V ;

Battista, S ;

Pentimalli, F ;

Klein-Szanto, AJP ;

Visone, R ;

De Martino, I ;

Curcio, A ;

Morisco, C ;

Del Vecchio, L ;

Baldassarre, G ;

Arra, C ;

Viglietto, G ;

Indolfi, C ;

Croce, CM ;

Fusco, A .

CANCER RESEARCH, 2006, 66 (05) :2536-2543

[14] Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell [J].

Fedele, M ;

Pentimalli, F ;

Baldassarre, G ;

Battista, S ;

Klein-Szanto, AJP ;

Kenyon, L ;

Visone, R ;

De Martino, I ;

Ciarmiello, A ;

Arra, C ;

Viglietto, G ;

Croce, CM ;

Fusco, A .

ONCOGENE, 2005, 24 (21) :3427-3435

[15] Gene expression profiling in T-cell acute lymphoblastic leukemia [J].

Ferrando, AA ;

Look, AT .

SEMINARS IN HEMATOLOGY, 2003, 40 (04) :274-280

[16] Roles of HMGA proteins in cancer [J].

Fusco, Alfredo ;

Fedele, Monica .

NATURE REVIEWS CANCER, 2007, 7 (12) :899-910

[17] Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia [J].

Grabher, C ;

von Boehmer, H ;

Look, AT .

NATURE REVIEWS CANCER, 2006, 6 (05) :347-359

[18]

Herman JG, 1997, CANCER RES, V57, P837

[19] The HMGA1-COX-2 axis: A key molecular pathway and potential target in pancreatic adenocarcinoma [J].

Hillion, Joelle ;

Smail, Shamayra S. ;

Di Cello, Francescopaolo ;

Belton, Amy ;

Shah, Sandeep N. ;

Huso, Tait ;

Schuldenfrei, Andrew ;

Nelson, Dwella Moton ;

Cope, Leslie ;

Campbell, Nathaniel ;

Karikari, Collins ;

Aderinto, Abimbola ;

Maitra, Anirban ;

Huso, David L. ;

Resar, Linda M. S. .

PANCREATOLOGY, 2012, 12 (04) :372-379

[20] Upregulation of MMP-2 by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer [J].

Hillion, Joelle ;

Wood, Lisa J. ;

Mukherjee, Mita ;

Bhattacharya, Raka ;

Di Cello, Francescopaolo ;

Kowalski, Jeanne ;

Elbahloul, Ossama ;

Segal, Jodi ;

Poirier, John ;

Rudin, Charles M. ;

Dhara, Surajit ;

Belton, Amy ;

Joseph, Biju ;

Zucker, Stanley ;

Resar, Linda M. S. .

MOLECULAR CANCER RESEARCH, 2009, 7 (11) :1803-1812

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