Iris T. Chan, Jeffery L. Kutok, Ifor R. Williams, Sarah Cohen, Ra Moore, Hirokazu Shigematsu, ...
Most patients with acute promyelocytic leukemia (APL) express PML-RAR�, the fusion product of t(15;17)(q22;q11.2). Transgenic mice expressing PML-RAR� develop APL with long latency, low...
Oncology, Departments of Medicine (2008)
Jessica L. Pollock, Andrew A. Lane, Kelly Schrimpf, Timothy J. Ley, Siteman Cancer
Murine acute promyelocytic leukemia cells can be recognized and cleared in vivo by adaptive immune mechanisms Background and Objectives. In this study, we tested whether transgenic murine acute...
Chang, Li Wei, Payton, Jacqueline E, Yuan, Wenlin, Ley, Timothy J, Nagarajan, Rakesh, Stormo, Gary D
Abstract Background Acute myeloid leukemia (AML) comprises a group of diseases characterized by the abnormal development of malignant myeloid cells. Recent studies have demonstrated an important role...
Cahan, Patrick, Godfrey, Laura E., Eis, Peggy S., Richmond, Todd A., Selzer, Rebecca R., Brent, Michael, ...
Copy number variants (CNVs) are currently defined as genomic sequences that are polymorphic in copy number and range in length from 1000 to several million base pairs. Among current array-based CNV...
The Physician-Scientist: Career Issues and Challenges at the Year 2000 (2007)
Tamara Zemlo Howard, Howard H. Garrison, Nicola C. Partridge, Timothy J. Ley
this report, we define physicianscientists as those individuals holding an M.D. or M.D./Ph.D. degree who perform biomedical research of any type as their primary professional activity. We include...
A High-Resolution Map of Segmental DNA Copy Number Variation in the Mouse Genome (2007)
Timothy A. Graubert, Patrick Cahan, Deepa Edwin, Rebecca R. Selzer, Todd A. Richmond, Peggy S. Eis, ...
Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants...
Wenlin Yuan, Jacqueline E Payton, Matthew S Holt, Daniel C Link, Mark A Watson, John F Dipersio, ...
doi:10.1182/blood-2006-07-036640 Commonly dysregulated genes in murine APL cells
Matthew J. Walter, John S. Park, Xia Li, Andrew A. Lane, Rakesh Nagarajan, ...
Leukemia results from the expansion of self-renewing hematopoietic cells that are thought to contain mutations that contribute to disease initiation and progression. Studies of the gene expression...
Neutrophil Elastase Is Important for PML-Retinoic Acid (2004)
Receptor Activities, Early Myeloid Cells, Andrew A. Lane, Timothy J. Ley
Expression of the PML-retinoic acid receptor � (PML-RAR�) fusion protein is the initiating genetic event for acute promyelocytic leukemia (APL), but the molecular mechanisms responsible for...
Structure and function of the murine {beta}-globin locus control region 5' HS-3 (1992)
Hug, Bruce A., Moon, Anne M., Ley, Timothy J.
We previously identified the murine homologue of the human β-globin Locus Control Region (LCR) 5′ HS-2. The λ clone containing murine 5′ HS-2 extends approximately 12 kb upstream from this...
Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo
Pham, Christine T. N., Ley, Timothy J.
Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of...
Pollock, Jessica L., Westervelt, Peter, Kurichety, Arun K., Pelicci, Pier Giuseppe, Grisolano, Jay L., Ley, Timothy J.
Acute promyelocytic leukemia (APML) most often is associated with the balanced reciprocal translocation t(15;17) (q22;q11.2) and the expression of both the PML-RARα and RARα-PML fusion cDNAs that...
Zimonjic, Drazen B., Pollock, Jessica L., Westervelt, Peter, Popescu, Nicholas C., Ley, Timothy J.
We previously generated a transgenic mouse model for acute promyelocytic leukemia (APL) by expressing the promyelocytic leukemia (PML)–retinoic acid receptor (RARα) cDNA in early myeloid cells....
Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK
Thomas, Dori A., Scorrano, Luca, Putcha, Girish V., Korsmeyer, Stanley J., Ley, Timothy J.
Granzyme B (GzmB) is a serine protease that is used by activated cytotoxic T lymphocytes to induce target cell apoptosis. Although GzmB directly cleaves the Bcl2 family member BID on target cell...
PML/RARα and FLT3-ITD induce an APL-like disease in a mouse model
Kelly, Louise M., Kutok, Jeffrey L., Williams, Ifor R., Boulton, Christina L., Amaral, Sonia M., Curley, David P., ...
Acute promyelocytic leukemia (APL) cells invariably express aberrant fusion proteins involving the retinoic acid receptor α (RARα). The most common fusion partner is promyelocytic leukemia protein...
Westervelt, Peter, Pollock, Jessica L., Oldfather, Kristie M., Walter, Matthew J., Ma, Margaret K., Williams, Anthony, ...
We previously developed a murine model of acute promyelocytic leukemia (APL) by using human cathepsin G gene regulatory elements to direct the expression of promyelocytic leukemia (PML)/retinoic acid...
Ley, Timothy J., Minx, Patrick J., Walter, Matthew J., Ries, Rhonda E., Sun, Hui, McLellan, Michael, ...
In this pilot study, we used primary human acute myeloid leukemia (AML) cell genomes as templates for exonic PCR amplification, followed by high-throughput resequencing, analyzing ≈7 million base...
A proteomic approach for the discovery of protease substrates
Bredemeyer, Andrew J., Lewis, Renate M., Malone, James P., Davis, Alan E., Gross, Julia, Townsend, R. Reid, ...
Standardized, comprehensive platforms for the discovery of protease substrates have been extremely difficult to create. Screens for protease specificity are now frequently based on the cleavage...
Granzymes and Caspase 3 Play Important Roles in Control of Gammaherpesvirus Latency
Loh, Joy, Thomas, Dori A., Revell, Paula A., Ley, Timothy J., Virgin, Herbert W.
Gammaherpesviruses can establish lifelong latent infections in lymphoid cells of their hosts despite active antiviral immunity. Identification of the immune mechanisms which regulate gammaherpesvirus...
Walter, Matthew J., Park, John S., Lau, Steven K. M., Li, Xia, Lane, Andrew A., Nagarajan, Rakesh, ...
Leukemia results from the expansion of self-renewing hematopoietic cells that are thought to contain mutations that contribute to disease initiation and progression. Studies of the gene expression...
Neutrophil Elastase Is Important for PML-Retinoic Acid Receptor α Activities in Early Myeloid Cells
Lane, Andrew A., Ley, Timothy J.
Expression of the PML-retinoic acid receptor α (PML-RARα) fusion protein is the initiating genetic event for acute promyelocytic leukemia (APL), but the molecular mechanisms responsible for disease...
Lu, Zhi Hong, Books, Jason T., Ley, Timothy J.
Proteins containing “cold shock” domains belong to the most evolutionarily conserved family of nucleic acid-binding proteins known among bacteria, plants, and animals. One of these proteins,...
Walter, Matthew J., Park, John S., Ries, Rhonda E., Lau, Steven K. M., McLellan, Michael, Jaeger, Sara, ...
PU.1 is a member of the ETS family of transcription factors that is known to be important for hematopoietic development. Recently, haploinsufficiency for PU.1 has been shown to cause a shift in...
Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo
Pham, Christine T. N., Ley, Timothy J.
Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of...
Pollock, Jessica L., Westervelt, Peter, Kurichety, Arun K., Pelicci, Pier Giuseppe, Grisolano, Jay L., Ley, Timothy J.
Acute promyelocytic leukemia (APML) most often is associated with the balanced reciprocal translocation t(15;17) (q22;q11.2) and the expression of both the PML-RARα and RARα-PML fusion cDNAs that...
Zimonjic, Drazen B., Pollock, Jessica L., Westervelt, Peter, Popescu, Nicholas C., Ley, Timothy J.
We previously generated a transgenic mouse model for acute promyelocytic leukemia (APL) by expressing the promyelocytic leukemia (PML)–retinoic acid receptor (RARα) cDNA in early myeloid cells....
Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK
Thomas, Dori A., Scorrano, Luca, Putcha, Girish V., Korsmeyer, Stanley J., Ley, Timothy J.
Granzyme B (GzmB) is a serine protease that is used by activated cytotoxic T lymphocytes to induce target cell apoptosis. Although GzmB directly cleaves the Bcl2 family member BID on target cell...
PML/RARα and FLT3-ITD induce an APL-like disease in a mouse model
Kelly, Louise M., Kutok, Jeffrey L., Williams, Ifor R., Boulton, Christina L., Amaral, Sonia M., Curley, David P., ...
Acute promyelocytic leukemia (APL) cells invariably express aberrant fusion proteins involving the retinoic acid receptor α (RARα). The most common fusion partner is promyelocytic leukemia protein...
Westervelt, Peter, Pollock, Jessica L., Oldfather, Kristie M., Walter, Matthew J., Ma, Margaret K., Williams, Anthony, ...
We previously developed a murine model of acute promyelocytic leukemia (APL) by using human cathepsin G gene regulatory elements to direct the expression of promyelocytic leukemia (PML)/retinoic acid...
Ley, Timothy J., Minx, Patrick J., Walter, Matthew J., Ries, Rhonda E., Sun, Hui, McLellan, Michael, ...
In this pilot study, we used primary human acute myeloid leukemia (AML) cell genomes as templates for exonic PCR amplification, followed by high-throughput resequencing, analyzing ≈7 million base...
A proteomic approach for the discovery of protease substrates
Bredemeyer, Andrew J., Lewis, Renate M., Malone, James P., Davis, Alan E., Gross, Julia, Townsend, R. Reid, ...
Standardized, comprehensive platforms for the discovery of protease substrates have been extremely difficult to create. Screens for protease specificity are now frequently based on the cleavage...
Granzymes and Caspase 3 Play Important Roles in Control of Gammaherpesvirus Latency
Loh, Joy, Thomas, Dori A., Revell, Paula A., Ley, Timothy J., Virgin, Herbert W.
Gammaherpesviruses can establish lifelong latent infections in lymphoid cells of their hosts despite active antiviral immunity. Identification of the immune mechanisms which regulate gammaherpesvirus...
Walter, Matthew J., Park, John S., Lau, Steven K. M., Li, Xia, Lane, Andrew A., Nagarajan, Rakesh, ...
Leukemia results from the expansion of self-renewing hematopoietic cells that are thought to contain mutations that contribute to disease initiation and progression. Studies of the gene expression...
Neutrophil Elastase Is Important for PML-Retinoic Acid Receptor α Activities in Early Myeloid Cells
Lane, Andrew A., Ley, Timothy J.
Expression of the PML-retinoic acid receptor α (PML-RARα) fusion protein is the initiating genetic event for acute promyelocytic leukemia (APL), but the molecular mechanisms responsible for disease...
Lu, Zhi Hong, Books, Jason T., Ley, Timothy J.
Proteins containing “cold shock” domains belong to the most evolutionarily conserved family of nucleic acid-binding proteins known among bacteria, plants, and animals. One of these proteins,...
Walter, Matthew J., Park, John S., Ries, Rhonda E., Lau, Steven K. M., McLellan, Michael, Jaeger, Sara, ...
PU.1 is a member of the ETS family of transcription factors that is known to be important for hematopoietic development. Recently, haploinsufficiency for PU.1 has been shown to cause a shift in...
A High-Resolution Map of Segmental DNA Copy Number Variation in the Mouse Genome
Graubert, Timothy A, Cahan, Patrick, Edwin, Deepa, Selzer, Rebecca R, Richmond, Todd A, Eis, Peggy S, ...
Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants...
Lu, Zhi Hong, Books, Jason T., Ley, Timothy J.
Three cold shock domain (CSD) family members (YB-1, MSY2, and MSY4) exist in vertebrate species ranging from frogs to humans. YB-1 is expressed throughout embryogenesis and is ubiquitously expressed...
Oncogenic K-ras cooperates with PML-RARα to induce an acute promyelocytic leukemia-like disease
Chan, Iris T., Kutok, Jeffery L., Williams, Ifor R., Cohen, Sarah, Moore, Sandra, Shigematsu, Hirokazu, ...
Most patients with acute promyelocytic leukemia (APL) express PML-RARα, the fusion product of t(15;17)(q22;q11.2). Transgenic mice expressing PML-RARα develop APL with long latency, low penetrance,...
Commonly dysregulated genes in murine APL cells
Yuan, Wenlin, Payton, Jacqueline E., Holt, Matthew S., Link, Daniel C., Watson, Mark A., DiPersio, John F., ...
To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial...
Walter, Matthew J., Ries, Rhonda E., Armstrong, Jon R., Park, John S., Mardis, Elaine R., Ley, Timothy J.
Expression of a bcr-3 isoform of retinoic acid receptor α–promyelocytic leukemia (RARα-PML) in mice expressing a bcr-1 isoform of PML-RARα is associated with increased penetrance of murine acute...
Chang, Li Wei, Payton, Jacqueline E, Yuan, Wenlin, Ley, Timothy J, Nagarajan, Rakesh, Stormo, Gary D
A dissection of the genetic networks and circuitries is described for two form of leukaemia. Integrating transcription factor binding and gene expression profiling, networks are revealed that underly...
Cahan, Patrick, Godfrey, Laura E., Eis, Peggy S., Richmond, Todd A., Selzer, Rebecca R., Brent, Michael, ...
Copy number variants (CNVs) are currently defined as genomic sequences that are polymorphic in copy number and range in length from 1000 to several million base pairs. Among current array-based CNV...
Link, Daniel C., Kunter, Ghada, Kasai, Yumi, Zhao, Yu, Miner, Tracie, McLellan, Michael D., ...
Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Like most other bone marrow failure syndromes, it is associated with a marked propensity to transform into a...
Tomasson, Michael H., Xiang, Zhifu, Walgren, Richard, Zhao, Yu, Kasai, Yumi, Miner, Tracie, ...
Activating mutations in tyrosine kinase (TK) genes (eg, FLT3 and KIT) are found in more than 30% of patients with de novo acute myeloid leukemia (AML); many groups have speculated that mutations in...
Identification of somatic JAK1 mutations in patients with acute myeloid leukemia
Xiang, Zhifu, Zhao, Yu, Mitaksov, Vesselin, Fremont, Daved H., Kasai, Yumi, Molitoris, AnnaLynn, ...
Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML...
Payton, Jacqueline E., Grieselhuber, Nicole R., Chang, Li-Wei, Murakami, Mark, Geiss, Gary K., Link, Daniel C., ...
Acute promyelocytic leukemia (APL) is characterized by the t(15;17) chromosomal translocation, which results in fusion of the retinoic acid receptor α (RARA) gene to another gene, most commonly...
Acquired copy number alterations in adult acute myeloid leukemia genomes
Walter, Matthew J., Payton, Jacqueline E., Ries, Rhonda E., Shannon, William D., Deshmukh, Hrishikesh, Zhao, Yu, ...
Cytogenetic analysis of acute myeloid leukemia (AML) cells has accelerated the identification of genes important for AML pathogenesis. To complement cytogenetic studies and to identify genes altered...
Funk, Ryan K., Maxwell, Taylor J., Izumi, Masayo, Edwin, Deepa, Kreisel, Friederike, Ley, Timothy J., ...
Therapy-related acute myelogenous leukemia (t-AML) is an important late adverse effect of alkylator chemotherapy. Susceptibility to t-AML has a genetic component, yet specific genetic variants that...