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TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , |
| In: | Proceedings of the National Academy of Sciences, 103, 2006, 41, S. 15166-15171 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. |
|---|---|
| author |
Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. |
| spellingShingle |
Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. Proceedings of the National Academy of Sciences TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia Multidisciplinary |
| author_sort |
sabaawy, hatem e. |
| spelling |
Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0603349103 <jats:p> Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The <jats:italic>TEL-AML1</jats:italic> ( <jats:italic>ETV6-RUNX1</jats:italic> ) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of <jats:italic>TEL-AML1</jats:italic> -induced leukemia have not been identified. To study the origin of <jats:italic>TEL-AML1</jats:italic> -induced ALL, we generated transgenic zebrafish expressing <jats:italic>TEL-AML1</jats:italic> either ubiquitously or in lymphoid progenitors. <jats:italic>TEL-AML1</jats:italic> expression in all lineages, but not lymphoid-restricted expression, led to progenitor cell expansion that evolved into oligoclonal B-lineage ALL in 3% of the transgenic zebrafish. This leukemia was transplantable to conditioned wild-type recipients. We demonstrate that <jats:italic>TEL-AML1</jats:italic> induces a B cell differentiation arrest, and that leukemia development is associated with loss of <jats:italic>TEL</jats:italic> expression and elevated <jats:italic>Bcl2</jats:italic> / <jats:italic>Bax</jats:italic> ratio. The <jats:italic>TEL-AML1</jats:italic> transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets. </jats:p> <i>TEL-AML1</i> transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia Proceedings of the National Academy of Sciences |
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10.1073/pnas.0603349103 |
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Proceedings of the National Academy of Sciences, 2006 |
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Proceedings of the National Academy of Sciences, 2006 |
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| title |
TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_unstemmed |
TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_full |
TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_fullStr |
TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_full_unstemmed |
TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_short |
TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_sort |
<i>tel-aml1</i>
transgenic zebrafish model of precursor b cell acute lymphoblastic leukemia |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.0603349103 |
| publishDate |
2006 |
| physical |
15166-15171 |
| description |
<jats:p>
Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The
<jats:italic>TEL-AML1</jats:italic>
(
<jats:italic>ETV6-RUNX1</jats:italic>
) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of
<jats:italic>TEL-AML1</jats:italic>
-induced leukemia have not been identified. To study the origin of
<jats:italic>TEL-AML1</jats:italic>
-induced ALL, we generated transgenic zebrafish expressing
<jats:italic>TEL-AML1</jats:italic>
either ubiquitously or in lymphoid progenitors.
<jats:italic>TEL-AML1</jats:italic>
expression in all lineages, but not lymphoid-restricted expression, led to progenitor cell expansion that evolved into oligoclonal B-lineage ALL in 3% of the transgenic zebrafish. This leukemia was transplantable to conditioned wild-type recipients. We demonstrate that
<jats:italic>TEL-AML1</jats:italic>
induces a B cell differentiation arrest, and that leukemia development is associated with loss of
<jats:italic>TEL</jats:italic>
expression and elevated
<jats:italic>Bcl2</jats:italic>
/
<jats:italic>Bax</jats:italic>
ratio. The
<jats:italic>TEL-AML1</jats:italic>
transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets.
</jats:p> |
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| author | Sabaawy, Hatem E., Azuma, Mizuki, Embree, Lisa J., Tsai, Huai-Jen, Starost, Matthew F., Hickstein, Dennis D. |
| author_facet | Sabaawy, Hatem E., Azuma, Mizuki, Embree, Lisa J., Tsai, Huai-Jen, Starost, Matthew F., Hickstein, Dennis D., Sabaawy, Hatem E., Azuma, Mizuki, Embree, Lisa J., Tsai, Huai-Jen, Starost, Matthew F., Hickstein, Dennis D. |
| author_sort | sabaawy, hatem e. |
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| description | <jats:p> Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The <jats:italic>TEL-AML1</jats:italic> ( <jats:italic>ETV6-RUNX1</jats:italic> ) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of <jats:italic>TEL-AML1</jats:italic> -induced leukemia have not been identified. To study the origin of <jats:italic>TEL-AML1</jats:italic> -induced ALL, we generated transgenic zebrafish expressing <jats:italic>TEL-AML1</jats:italic> either ubiquitously or in lymphoid progenitors. <jats:italic>TEL-AML1</jats:italic> expression in all lineages, but not lymphoid-restricted expression, led to progenitor cell expansion that evolved into oligoclonal B-lineage ALL in 3% of the transgenic zebrafish. This leukemia was transplantable to conditioned wild-type recipients. We demonstrate that <jats:italic>TEL-AML1</jats:italic> induces a B cell differentiation arrest, and that leukemia development is associated with loss of <jats:italic>TEL</jats:italic> expression and elevated <jats:italic>Bcl2</jats:italic> / <jats:italic>Bax</jats:italic> ratio. The <jats:italic>TEL-AML1</jats:italic> transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets. </jats:p> |
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| imprint | Proceedings of the National Academy of Sciences, 2006 |
| imprint_str_mv | Proceedings of the National Academy of Sciences, 2006 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
| issn | 1091-6490, 0027-8424 |
| issn_str_mv | 1091-6490, 0027-8424 |
| language | English |
| last_indexed | 2024-03-01T17:47:48.899Z |
| match_str | sabaawy2006telaml1transgeniczebrafishmodelofprecursorbcellacutelymphoblasticleukemia |
| mega_collection | Proceedings of the National Academy of Sciences (CrossRef) |
| physical | 15166-15171 |
| publishDate | 2006 |
| publishDateSort | 2006 |
| publisher | Proceedings of the National Academy of Sciences |
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| series | Proceedings of the National Academy of Sciences |
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| spelling | Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0603349103 <jats:p> Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The <jats:italic>TEL-AML1</jats:italic> ( <jats:italic>ETV6-RUNX1</jats:italic> ) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of <jats:italic>TEL-AML1</jats:italic> -induced leukemia have not been identified. To study the origin of <jats:italic>TEL-AML1</jats:italic> -induced ALL, we generated transgenic zebrafish expressing <jats:italic>TEL-AML1</jats:italic> either ubiquitously or in lymphoid progenitors. <jats:italic>TEL-AML1</jats:italic> expression in all lineages, but not lymphoid-restricted expression, led to progenitor cell expansion that evolved into oligoclonal B-lineage ALL in 3% of the transgenic zebrafish. This leukemia was transplantable to conditioned wild-type recipients. We demonstrate that <jats:italic>TEL-AML1</jats:italic> induces a B cell differentiation arrest, and that leukemia development is associated with loss of <jats:italic>TEL</jats:italic> expression and elevated <jats:italic>Bcl2</jats:italic> / <jats:italic>Bax</jats:italic> ratio. The <jats:italic>TEL-AML1</jats:italic> transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets. </jats:p> <i>TEL-AML1</i> transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia Proceedings of the National Academy of Sciences |
| spellingShingle | Sabaawy, Hatem E., Azuma, Mizuki, Embree, Lisa J., Tsai, Huai-Jen, Starost, Matthew F., Hickstein, Dennis D., Proceedings of the National Academy of Sciences, TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia, Multidisciplinary |
| title | TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_full | TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_fullStr | TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_full_unstemmed | TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_short | TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| title_sort | <i>tel-aml1</i> transgenic zebrafish model of precursor b cell acute lymphoblastic leukemia |
| title_unstemmed | TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.0603349103 |