Genetic profile of T-cell acute lymphoblastic leukemias with MYC translocations

被引：46

作者：

La Starza, Roberta ^{[1
]}

Borga, Chiara ^{[2
]}

Barba, Gianluca ^{[1
]}

Pierini, Valentina ^{[1
]}

Schwab, Claire ^{[3
]}

Matteucci, Caterina ^{[1
]}

Fernandez, Anair G. Lema ^{[1
]}

Leszl, Anna ^{[2
]}

Cazzaniga, Gianni ^{[4
]}

Chiaretti, Sabina ^{[5
]}

Basso, Giuseppe ^{[2
]}

Harrison, Christine J. ^{[3
]}

te Kronnie, Geertruy ^{[2
]}

Mecucci, Cristina ^{[1
]}

机构：

[1] Univ Perugia, Hematol Unit, Polo Unico SM Misericordia, I-06156 Perugia, Italy

[2] Univ Padua, Dept Womens & Childrens Hlth, Padua, Italy

[3] Newcastle Univ, Leukaemia Res Cytogenet Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[4] Univ Milano Bicocca, Pediat Clin, Ctr Ric Tettamanti, Monza, Italy

[5] Univ Roma La Sapienza, Div Hematol, I-00185 Rome, Italy

来源：

BLOOD | 2014年 / 124卷 / 24期

关键词：

PTEN; ACTIVATION; INHIBITION; EXPRESSION; ZEBRAFISH; PATHWAY; PTPN2; MICE;

D O I：

10.1182/blood-2014-06-578856

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

MYC translocations represent a genetic subtype of T-lineage acute lymphoblastic leukemia (T-ALL), which occurs at an incidence of similar to 6%, assessed within a cohort of 196 T-ALL patients (64 adults and 132 children). The translocations were of 2 types; those rearranged with the T-cell receptor loci and those with other partners. MYC translocations were significantly associated with the TAL/LMO subtype of T-ALL (P=.018) and trisomies 6 (P < .001) and 7 (P < .001). Within the TAL/LMO subtype, gene expression profiling identified 148 differentially expressed genes between patients with and without MYC translocations; specifically, 77 were upregulated and 71 downregulated in those with MYC translocations. The poor prognostic marker, CD44, was among the upregulated genes. MYC translocations occurred as secondary abnormalities, present in subclones in one-half of the cases. Longitudinal studies indicated an association with induction failure and relapse.

引用

页码：3577 / 3582

页数：6

共 25 条

[1] Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas [J].

Bertrand, P. ;

Bastard, C. ;

Maingonnat, C. ;

Jardin, F. ;

Maisonneuve, C. ;

Courel, M-N ;

Ruminy, P. ;

Picquenot, J-M ;

Tilly, H. .

LEUKEMIA, 2007, 21 (03) :515-523

[2] Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia [J].

Bonnet, Melanie ;

Loosveld, Marie ;

Montpellier, Bertrand ;

Navarro, Jean-Marc ;

Quilichini, Benoit ;

Picard, Christophe ;

Di Cristofaro, Julie ;

Bagnis, Claude ;

Fossat, Chantal ;

Hernandez, Lucie ;

Mamessier, Emilie ;

Roulland, Sandrine ;

Morgado, Ester ;

Formisano-Treziny, Christine ;

Dik, Willem A. ;

Langerak, Anton W. ;

Prebet, Thomas ;

Vey, Norbert ;

Michel, Gerard ;

Gabert, Jean ;

Soulier, Jean ;

Macintyre, Elizabeth A. ;

Asnafi, Vahid ;

Payet-Bornet, Dominique ;

Nadel, Bertrand .

BLOOD, 2011, 117 (24) :6650-6659

[3] Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia [J].

Cario, G ;

Stanulla, M ;

Fine, BM ;

Teuffel, O ;

Neuhoff, NV ;

Schrauder, A ;

Flohr, T ;

Schaier, BW ;

Bartram, CR ;

Welte, K ;

Schlegelberger, B ;

Schrappe, M .

BLOOD, 2005, 105 (02) :821-826

[4] Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse [J].

Clappier, Emmanuelle ;

Gerby, Bastien ;

Sigaux, Francois ;

Delord, Marc ;

Touzri, Farah ;

Hernandez, Lucie ;

Ballerini, Paola ;

Baruchel, Andre ;

Pflumio, Francoise ;

Soulier, Jean .

JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (04) :653-661

[5] New markers for minimal residual disease detection in acute lymphoblastic leukemia [J].

Coustan-Smith, Elaine ;

Song, Guangchun ;

Clark, Christopher ;

Key, Laura ;

Liu, Peixin ;

Mehrpooya, Mohammad ;

Stow, Patricia ;

Su, Xiaoping ;

Shurtleff, Sheila ;

Pui, Ching-Hon ;

Downing, James R. ;

Campana, Dario .

BLOOD, 2011, 117 (23) :6267-6276

[6] Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing [J].

Ding, Li ;

Ley, Timothy J. ;

Larson, David E. ;

Miller, Christopher A. ;

Koboldt, Daniel C. ;

Welch, John S. ;

Ritchey, Julie K. ;

Young, Margaret A. ;

Lamprecht, Tamara ;

McLellan, Michael D. ;

McMichael, Joshua F. ;

Wallis, John W. ;

Lu, Charles ;

Shen, Dong ;

Harris, Christopher C. ;

Dooling, David J. ;

Fulton, Robert S. ;

Fulton, Lucinda L. ;

Chen, Ken ;

Schmidt, Heather ;

Kalicki-Veizer, Joelle ;

Magrini, Vincent J. ;

Cook, Lisa ;

McGrath, Sean D. ;

Vickery, Tammi L. ;

Wendl, Michael C. ;

Heath, Sharon ;

Watson, Mark A. ;

Link, Daniel C. ;

Tomasson, Michael H. ;

Shannon, William D. ;

Payton, Jacqueline E. ;

Kulkarni, Shashikant ;

Westervelt, Peter ;

Walter, Matthew J. ;

Graubert, Timothy A. ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

DiPersio, John F. .

NATURE, 2012, 481 (7382) :506-510

[7] Selective inhibition of BET bromodomains [J].

Filippakopoulos, Panagis ;

Qi, Jun ;

Picaud, Sarah ;

Shen, Yao ;

Smith, William B. ;

Fedorov, Oleg ;

Morse, Elizabeth M. ;

Keates, Tracey ;

Hickman, Tyler T. ;

Felletar, Ildiko ;

Philpott, Martin ;

Munro, Shonagh ;

McKeown, Michael R. ;

Wang, Yuchuan ;

Christie, Amanda L. ;

West, Nathan ;

Cameron, Michael J. ;

Schwartz, Brian ;

Heightman, Tom D. ;

La Thangue, Nicholas ;

French, Christopher A. ;

Wiest, Olaf ;

Kung, Andrew L. ;

Knapp, Stefan ;

Bradner, James E. .

NATURE, 2010, 468 (7327) :1067-1073

[8] Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation [J].

Guo, Wei ;

Lasky, Joseph L. ;

Chang, Chun-Ju ;

Mosessian, Sherly ;

Lewis, Xiaoman ;

Xiao, Yun ;

Yeh, Jennifer E. ;

Chen, James Y. ;

Iruela-Arispe, M. Luisa ;

Varella-Garcia, Marileila ;

Wu, Hong .

NATURE, 2008, 453 (7194) :529-U7

[9] Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia [J].

Gutierrez, Alejandro ;

Grebliunaite, Ruta ;

Feng, Hui ;

Kozakewich, Elena ;

Zhu, Shizhen ;

Guo, Feng ;

Payne, Elspeth ;

Mansour, Marc ;

Dahlberg, Suzanne E. ;

Neuberg, Donna S. ;

den Hertog, Jeroen ;

Prochownik, Edward V. ;

Testa, Joseph R. ;

Harris, Marian ;

Kanki, John P. ;

Look, A. Thomas .

JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (08) :1595-1603

[10] β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL [J].

Kaveri, Deepika ;

Kastner, Philippe ;

Dembele, Doulaye ;

Nerlov, Claus ;

Chan, Susan ;

Kirstetter, Peggy .

BLOOD, 2013, 122 (05) :694-704

← 1 2 3 →