A. Thomas Look

CHK1 inhibition as a strategy for targeting fanconi anemia (FA) DNA repair pathway deficient tumors (2009)

Chen, Clark C, Kennedy, Richard D, Sidi, Samuel, Look, A Thomas, D'Andrea, Alan

Abstract Background DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyper-dependent on DNA damage response pathways,...

The kinesin KIF1B{beta} acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor (2008)

Schlisio, Susanne, Kenchappa, Rajappa S., Vredeveld, Liesbeth C.W., George, Rani E., Stewart, Rodney, Greulich, Heidi, ...

VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells...

Alu elements mediate MYB gene tandem duplication in human T-ALL (2007)

O'Neil, Jennifer Elinor, Tchinda, Joelle, Gutierrez, Alejandro, Moreau, Lisa A., Maser, Richard S., Wong, Kwok-Kin, ...

Recent studies have demonstrated that the MYB oncogene is frequently duplicated in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB locus is flanked by 257-bp Alu repeats...

A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors (2007)

Smolen, Gromoslaw A., Schott, Benjamin J., Stewart, Rodney A., Diederichs, Sven, Muir, Beth, Provencher, Heather L., ...

The neural crest (NC) is a highly motile cell population that gives rise to multiple tissue lineages during vertebrate embryogenesis. Here, we identify a novel effector of the small GTPase Rap,...

Identification of structural aberrations in cancer by SNP array analysis (2007)

Heinrichs, Stefan, Look, A Thomas

Abstract Recent studies using single-nucleotide polymorphism arrays have pinpointed novel oncogenes and tumor suppressors involved in specific types of human cancers.

Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation (2007)

Guo, Zhuyan, Dose, Marei, Kovalovsky, Damian, Chang, Rui, O'Neil, Jennifer Elinor, Look, A. Thomas, ...

Activation of beta-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T cells promotes thymocyte development without the...

Activating Notch1 mutations in mouse models of T-ALL (2005)

O'Neil, Jennifer Elinor, Calvo, Jennifer Ann, McKenna, Keith, Krishnamoorthy, Veena, Aster, Jon C., Bassing, Craig H., ...

Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also...

Oncogenic transcription factors in the human acute leukemias (1997)

A. Thomas Look

Chromosomal translocations in the human acute leukemias rearrange the regulatory and coding regions of a variety of transcription factor genes. The resultant protein products can interfere with...

Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes

Ikushima, Satoshi, Inukai, Takeshi, Inaba, Toshiya, Nimer, Stephen D., Cleveland, John L., Look, A. Thomas

The E2A-HLF (hepatic leukemia factor) oncoprotein, generated in pro-B lymphocytes by fusion of the trans-activation domain of E2A to the basic region/leucine zipper (bZIP) domain of HLF, functions as...

Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome

Nichols, Kim E., Harkin, D. Paul, Levitz, Seth, Krainer, Michael, Kolquist, Kathryn Ann, Genovese, Cameo, ...

X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein–Barr virus (EBV). In affected males, primary EBV infection leads to...

Two Distinct Interleukin-3-Mediated Signal Pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, Regulate the Survival of Murine Pro-B Lymphocytes

Kuribara, Ryoko, Kinoshita, Taisei, Miyajima, Atsushi, Shinjyo, Tetsuharu, Yoshihara, Takao, Inukai, Takeshi, ...

Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely...

Downregulation of Bim, a Proapoptotic Relative of Bcl-2, Is a Pivotal Step in Cytokine-Initiated Survival Signaling in Murine Hematopoietic Progenitors

Shinjyo, Tetsuharu, Kuribara, Ryoko, Inukai, Takeshi, Hosoi, Hajime, Kinoshita, Taisei, Miyajima, Atsushi, ...

Two distinct signaling pathways regulate the survival of interleukin-3 (IL-3)-dependent hematopoietic progenitors. One originates from the membrane-proximal portion of the cytoplasmic domain of the...

The E2A-HLF Oncoprotein Activates Groucho-Related Genes and Suppresses Runx1

Dang, Jinjun, Inukai, Takeshi, Kurosawa, Hidemitsu, Goi, Kumiko, Inaba, Toshiya, Lenny, Noel T., ...

The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A...

Myb-Related Schizosaccharomyces pombe cdc5p Is Structurally and Functionally Conserved in Eukaryotes

Ohi, Ryoma, Feoktistova, Anna, McCann, Stacey, Valentine, Virginia, Look, A. Thomas, Lipsick, Joseph S., ...

Schizosaccharomyces pombe cdc5p is a Myb-related protein that is essential for G2/M progression. To explore the structural and functional conservation of Cdc5 throughout evolution, we isolated...

The AD1 and AD2 Transactivation Domains of E2A Are Essential for the Antiapoptotic Activity of the Chimeric Oncoprotein E2A-HLF

Inukai, Takeshi, Inaba, Toshiya, Ikushima, Satoshi, Look, A. Thomas

The chimeric oncoprotein E2A-HLF, generated by the t(17;19) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia, incorporates the transactivation domains of E2A and the basic leucine...

Evolutionary conservation of zebrafish linkage group 14 with frequently deleted regions of human chromosome 5 in myeloid malignancies

Liu, Ting Xi, Zhou, Yi, Kanki, John P., Deng, Min, Rhodes, Jennifer, Yang, Hong Wei, ...

Recurring interstitial loss of all or part of the long arm of chromosome 5, del(5q), is a hallmark of myelodysplastic syndrome and acute myeloid leukemia. Although the genes affected by these changes...

In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish

Langenau, David M., Ferrando, Adolfo A., Traver, David, Kutok, Jeffery L., Hezel, John-Paul D., Kanki, John P., ...

Transgenic zebrafish that express GFP under control of the T cell-specific tyrosine kinase (lck) promoter were used to analyze critical aspects of the immune system, including patterns of T cell...

Hematopoietic gene expression profile in zebrafish kidney marrow

Song, Huai-Dong, Sun, Xiao-Jian, Deng, Min, Zhang, Guo-Wei, Zhou, Yi, Wu, Xin-Yan, ...

The zebrafish kidney marrow is considered to be the organ of definitive hematopoiesis, analogous to the mammalian bone marrow. We have sequenced 26,143 ESTs and isolated 304 cDNAs with putative...

tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors

Berghmans, Stéphane, Murphey, Ryan D., Wienholds, Erno, Neuberg, Donna, Kutok, Jeffery L., Fletcher, Christopher D. M., ...

TP53 is the most frequently mutated tumor suppressor gene in human cancer, with nearly 50% of all tumors exhibiting a loss-of-function mutation. To further elucidate the genetic pathways involving...

Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia

Langenau, David M., Feng, Hui, Berghmans, Stephane, Kanki, John P., Kutok, Jeffery L., Look, A. Thomas

We have created a stable transgenic rag2-EGFP-mMyc zebrafish line that develops GFP-labeled T cell acute lymphoblastic leukemia (T-ALL), allowing visualization of the onset and spread of this...

Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study1

Mathew, Prasad, Valentine, Marcus B, Bowman, Laura C, Rowe, Susan T, Nash, Michael B, Valentine, Virginia A, ...

To assess the utility of fluorescence in situ hybridization (FISH) for analysis of MYCN gene amplification in neuroblastoma, we compared this assay with Southern blot analysis using tumor specimens...

p27KIP1 Deletions in Childhood Acute Lymphoblastic Leukemia

Komuro, Hiroaki, Valentine, Marcus B, Rubnitz, Jeffrey E, Saito, Midori, Raimondi, Susana C, Carroll, Andrew J, ...

The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations...

Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes

Ikushima, Satoshi, Inukai, Takeshi, Inaba, Toshiya, Nimer, Stephen D., Cleveland, John L., Look, A. Thomas

The E2A-HLF (hepatic leukemia factor) oncoprotein, generated in pro-B lymphocytes by fusion of the trans-activation domain of E2A to the basic region/leucine zipper (bZIP) domain of HLF, functions as...

Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome

Nichols, Kim E., Harkin, D. Paul, Levitz, Seth, Krainer, Michael, Kolquist, Kathryn Ann, Genovese, Cameo, ...

X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein–Barr virus (EBV). In affected males, primary EBV infection leads to...

Two Distinct Interleukin-3-Mediated Signal Pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, Regulate the Survival of Murine Pro-B Lymphocytes

Kuribara, Ryoko, Kinoshita, Taisei, Miyajima, Atsushi, Shinjyo, Tetsuharu, Yoshihara, Takao, Inukai, Takeshi, ...

Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely...

Downregulation of Bim, a Proapoptotic Relative of Bcl-2, Is a Pivotal Step in Cytokine-Initiated Survival Signaling in Murine Hematopoietic Progenitors

Shinjyo, Tetsuharu, Kuribara, Ryoko, Inukai, Takeshi, Hosoi, Hajime, Kinoshita, Taisei, Miyajima, Atsushi, ...

Two distinct signaling pathways regulate the survival of interleukin-3 (IL-3)-dependent hematopoietic progenitors. One originates from the membrane-proximal portion of the cytoplasmic domain of the...

The E2A-HLF Oncoprotein Activates Groucho-Related Genes and Suppresses Runx1

Dang, Jinjun, Inukai, Takeshi, Kurosawa, Hidemitsu, Goi, Kumiko, Inaba, Toshiya, Lenny, Noel T., ...

The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A...

Myb-Related Schizosaccharomyces pombe cdc5p Is Structurally and Functionally Conserved in Eukaryotes

Ohi, Ryoma, Feoktistova, Anna, McCann, Stacey, Valentine, Virginia, Look, A. Thomas, Lipsick, Joseph S., ...

Schizosaccharomyces pombe cdc5p is a Myb-related protein that is essential for G2/M progression. To explore the structural and functional conservation of Cdc5 throughout evolution, we isolated...

The AD1 and AD2 Transactivation Domains of E2A Are Essential for the Antiapoptotic Activity of the Chimeric Oncoprotein E2A-HLF

Inukai, Takeshi, Inaba, Toshiya, Ikushima, Satoshi, Look, A. Thomas

The chimeric oncoprotein E2A-HLF, generated by the t(17;19) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia, incorporates the transactivation domains of E2A and the basic leucine...

Evolutionary conservation of zebrafish linkage group 14 with frequently deleted regions of human chromosome 5 in myeloid malignancies

Liu, Ting Xi, Zhou, Yi, Kanki, John P., Deng, Min, Rhodes, Jennifer, Yang, Hong Wei, ...

Recurring interstitial loss of all or part of the long arm of chromosome 5, del(5q), is a hallmark of myelodysplastic syndrome and acute myeloid leukemia. Although the genes affected by these changes...

In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish

Langenau, David M., Ferrando, Adolfo A., Traver, David, Kutok, Jeffery L., Hezel, John-Paul D., Kanki, John P., ...

Transgenic zebrafish that express GFP under control of the T cell-specific tyrosine kinase (lck) promoter were used to analyze critical aspects of the immune system, including patterns of T cell...

Hematopoietic gene expression profile in zebrafish kidney marrow

Song, Huai-Dong, Sun, Xiao-Jian, Deng, Min, Zhang, Guo-Wei, Zhou, Yi, Wu, Xin-Yan, ...

The zebrafish kidney marrow is considered to be the organ of definitive hematopoiesis, analogous to the mammalian bone marrow. We have sequenced 26,143 ESTs and isolated 304 cDNAs with putative...

tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors

Berghmans, Stéphane, Murphey, Ryan D., Wienholds, Erno, Neuberg, Donna, Kutok, Jeffery L., Fletcher, Christopher D. M., ...

TP53 is the most frequently mutated tumor suppressor gene in human cancer, with nearly 50% of all tumors exhibiting a loss-of-function mutation. To further elucidate the genetic pathways involving...

Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia

Langenau, David M., Feng, Hui, Berghmans, Stephane, Kanki, John P., Kutok, Jeffery L., Look, A. Thomas

We have created a stable transgenic rag2-EGFP-mMyc zebrafish line that develops GFP-labeled T cell acute lymphoblastic leukemia (T-ALL), allowing visualization of the onset and spread of this...

Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study1

Mathew, Prasad, Valentine, Marcus B, Bowman, Laura C, Rowe, Susan T, Nash, Michael B, Valentine, Virginia A, ...

To assess the utility of fluorescence in situ hybridization (FISH) for analysis of MYCN gene amplification in neuroblastoma, we compared this assay with Southern blot analysis using tumor specimens...

p27KIP1 Deletions in Childhood Acute Lymphoblastic Leukemia

Komuro, Hiroaki, Valentine, Marcus B, Rubnitz, Jeffrey E, Saito, Midori, Raimondi, Susana C, Carroll, Andrew J, ...

The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations...

Lack of Homozygously Inactivated p73 in Single-Copy MYCN Primary Neuroblastomas and Neuroblastoma Cell Lines1

Kong, Xiao-Tang, Valentine, Virginia A, Rowe, Susan T, Valentine, Marcus B, Ragsdale, Susan T, Jones, Bart G, ...

We examined 18 neuroblastoma cell lines and 32 primary single-copy MYCN tumor specimens to determine whether mutations of p73, a novel p53-related gene located in chromosome band 1p36.33, contribute...

NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth

Palomero, Teresa, Lim, Wei Keat, Odom, Duncan T., Sulis, Maria Luisa, Real, Pedro J., Margolin, Adam, ...

The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T cell development and in the pathogenesis over...

cDNA Cloning, Expression Pattern, and Chromosomal Localization of Mlf1, Murine Homologue of a Gene Involved in Myelodysplasia and Acute Myeloid Leukemia

Hitzler, Johann K., Witte, David P., Jenkins, Nancy A., Copeland, Neal G., Gilbert, Debra J., Naeve, Clayton W., ...

The NPM-MLF1 fusion protein is expressed in blasts from patients with myelodysplasia/acute myeloid leukemia (MDS/AML) containing the t(3;5) chromosomal rearrangement. Nucleophosmin (NPM), a...

The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia

Levine, Ross L., Loriaux, Marc, Huntly, Brian J. P., Loh, Mignon L., Beran, Miroslav, Stoffregen, Eric, ...

Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation...

Activating Notch1 mutations in mouse models of T-ALL

O'Neil, Jennifer, Calvo, Jennifer, McKenna, Keith, Krishnamoorthy, Veena, Aster, Jon C., Bassing, Craig H., ...

Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also...

Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia

Palomero, Teresa, Odom, Duncan T., O'Neil, Jennifer, Ferrando, Adolfo A., Margolin, Adam, Neuberg, Donna S., ...

Aberrant expression of 1 or more transcription factor oncogenes is a critical component of the molecular pathogenesis of human T-cell acute lymphoblastic leukemia (T-ALL); however, oncogenic...

FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors

O'Neil, Jennifer, Grim, Jonathan, Strack, Peter, Rao, Sudhir, Tibbitts, Deanne, Winter, Christopher, ...

γ-secretase inhibitors (GSIs) can block NOTCH receptor signaling in vitro and therefore offer an attractive targeted therapy for tumors dependent on deregulated NOTCH activity. To clarify the basis...

A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors

Smolen, Gromoslaw A., Schott, Benjamin J., Stewart, Rodney A., Diederichs, Sven, Muir, Beth, Provencher, Heather L., ...

The neural crest (NC) is a highly motile cell population that gives rise to multiple tissue lineages during vertebrate embryogenesis. Here, we identify a novel effector of the small GTPase Rap,...

The BCL2A1 gene as a pre–T cell receptor–induced regulator of thymocyte survival

Mandal, Malay, Borowski, Christine, Palomero, Teresa, Ferrando, Adolfo A., Oberdoerffer, Philipp, Meng, Fanyong, ...

The pre–T cell receptor (TCR) is expressed early during T cell development and imposes a tight selection for differentiating T cell progenitors. Pre-TCR–expressing cells are selected to survive...

Identification of structural aberrations in cancer by SNP array analysis

Heinrichs, Stefan, Look, A Thomas

SNP microarrays are a powerful way of uncovering mutations relevant to cancer.

β-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation

Guo, Zhuyan, Dose, Marei, Kovalovsky, Damian, Chang, Rui, O'Neil, Jennifer, Look, A. Thomas, ...

Activation of β-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T cells promotes thymocyte development without the requirement...

Alu elements mediate MYB gene tandem duplication in human T-ALL

O'Neil, Jennifer, Tchinda, Joelle, Gutierrez, Alejandro, Moreau, Lisa, Maser, Richard S., Wong, Kwok-Kin, ...

Recent studies have demonstrated that the MYB oncogene is frequently duplicated in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB locus is flanked by 257-bp Alu repeats...

The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor

Schlisio, Susanne, Kenchappa, Rajappa S., Vredeveld, Liesbeth C.W., George, Rani E., Stewart, Rodney, Greulich, Heidi, ...

VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells...

Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias

Kim, Woo Jae, Okimoto, Ross A., Purton, Louise E., Goodwin, Meagan, Haserlat, Sara M., Dayyani, Farshid, ...

Ceramide is a lipid second messenger derived from the hydrolysis of sphingomyelin by sphingomyelinases (SMases) and implicated in diverse cellular responses, including growth arrest, differentiation,...