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ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms

(2019) HAEMATOLOGICA. 104(8). p.1608-1616
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Abstract
ZEB1 and ZEB2 are structurally related E-box binding homeobox transcription factors that induce epithelial to mesenchymal transitions during development and disease. As such, they regulate cancer cell invasion, dissemination and metastasis of solid tumors. In addition, their expression is associated with the gain of cancer stem cell properties and resistance to therapy. Using conditional loss-of-function mice, we previously demonstrated that Zeb2 also plays pivotal roles in hematopoiesis, controlling important cell fate decisions, lineage commitment and fidelity. In addition, upon Zeb2 overexpression, mice spontaneously develop immature T-cell lymphoblastic leukemia. Here we show that pre-leukemic Zeb2-overexpressing thymocytes are characterized by a differentiation delay at beta-selection due to aberrant activation of the interleukin-7 receptor signaling pathway. Notably, and in contrast to Lmo2-overexpressing thymocytes, these pre-leukemic Zeb2-overexpressing T-cell progenitors display no acquired self-renewal properties. Finally, Zeb2 activation in more differentiated T-cell precursor cells can also drive malignant T-cell development, suggesting that the early T-cell differentiation delay is not essential for Zeb2-mediated leukemic transformation. Altogether, our data suggest that Zeb2 and Lmo2 drive malignant transformation of immature T-cell progenitors via distinct molecular mechanisms.
Keywords
TRANSCRIPTION FACTORS, TERMINAL DIFFERENTIATION, TRANSGENIC MICE, E-CADHERIN, EXPRESSION, IL-7, EMT, PROTEINS, FAMILY, MODEL

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MLA
Goossens, Steven, et al. “ZEB2 and LMO2 Drive Immature T-Cell Lymphoblastic Leukemia via Distinct Oncogenic Mechanisms.” HAEMATOLOGICA, vol. 104, no. 8, 2019, pp. 1608–16.
APA
Goossens, S., Wang, J., Tremblay, C., De Medts, J., T’Sas, S., Nguyen, T., … Haigh, J. J. (2019). ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms. HAEMATOLOGICA, 104(8), 1608–1616.
Chicago author-date
Goossens, Steven, Jueqiong Wang, Cedric Tremblay, Jelle De Medts, Sara T’Sas, Thao Nguyen, Jesslyn Saw, et al. 2019. “ZEB2 and LMO2 Drive Immature T-Cell Lymphoblastic Leukemia via Distinct Oncogenic Mechanisms.” HAEMATOLOGICA 104 (8): 1608–16.
Chicago author-date (all authors)
Goossens, Steven, Jueqiong Wang, Cedric Tremblay, Jelle De Medts, Sara T’Sas, Thao Nguyen, Jesslyn Saw, Katharina Haigh, David J Curtis, Pieter Van Vlierberghe, Geert Berx, Tom Taghon, and Jody J Haigh. 2019. “ZEB2 and LMO2 Drive Immature T-Cell Lymphoblastic Leukemia via Distinct Oncogenic Mechanisms.” HAEMATOLOGICA 104 (8): 1608–1616.
Vancouver
1.
Goossens S, Wang J, Tremblay C, De Medts J, T’Sas S, Nguyen T, et al. ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms. HAEMATOLOGICA. 2019;104(8):1608–16.
IEEE
[1]
S. Goossens et al., “ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms,” HAEMATOLOGICA, vol. 104, no. 8, pp. 1608–1616, 2019.
@article{8591823,
  abstract     = {ZEB1 and ZEB2 are structurally related E-box binding homeobox transcription factors that induce epithelial to mesenchymal transitions during development and disease. As such, they regulate cancer cell invasion, dissemination and metastasis of solid tumors. In addition, their expression is associated with the gain of cancer stem cell properties and resistance to therapy. Using conditional loss-of-function mice, we previously demonstrated that Zeb2 also plays pivotal roles in hematopoiesis, controlling important cell fate decisions, lineage commitment and fidelity. In addition, upon Zeb2 overexpression, mice spontaneously develop immature T-cell lymphoblastic leukemia. Here we show that pre-leukemic Zeb2-overexpressing thymocytes are characterized by a differentiation delay at beta-selection due to aberrant activation of the interleukin-7 receptor signaling pathway. Notably, and in contrast to Lmo2-overexpressing thymocytes, these pre-leukemic Zeb2-overexpressing T-cell progenitors display no acquired self-renewal properties. Finally, Zeb2 activation in more differentiated T-cell precursor cells can also drive malignant T-cell development, suggesting that the early T-cell differentiation delay is not essential for Zeb2-mediated leukemic transformation. Altogether, our data suggest that Zeb2 and Lmo2 drive malignant transformation of immature T-cell progenitors via distinct molecular mechanisms.},
  author       = {Goossens, Steven and Wang, Jueqiong and Tremblay, Cedric and De Medts, Jelle and T'Sas, Sara and Nguyen, Thao and Saw, Jesslyn and Haigh, Katharina and Curtis, David J and Van Vlierberghe, Pieter and Berx, Geert and Taghon, Tom and Haigh, Jody J},
  issn         = {0390-6078},
  journal      = {HAEMATOLOGICA},
  keywords     = {TRANSCRIPTION FACTORS,TERMINAL DIFFERENTIATION,TRANSGENIC MICE,E-CADHERIN,EXPRESSION,IL-7,EMT,PROTEINS,FAMILY,MODEL},
  language     = {eng},
  number       = {8},
  pages        = {1608--1616},
  title        = {ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms},
  url          = {http://dx.doi.org/10.3324/haematol.2018.207837},
  volume       = {104},
  year         = {2019},
}

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