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Pretz, Jennifer

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Pretz

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Jennifer

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Pretz, Jennifer
Author's Publications: search.filters.isAuthorOfPublication.1f205bf6-edd4-41c5-940d-7b61ca320ffa

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    MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors
    (Elsevier BV, 2008) Lu, Jun; Guo, Shangqin; Ebert, Benjamin; Zhang, Hao; Peng, Xiao; Bosco, Jocelyn; Pretz, Jennifer; Schlanger, Rita; Wang, Judy Y.; Mak, Raymond; Dombkowski, David M.; Preffer, Frederic; Scadden, David; Golub, Todd
    Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in that process and used the poorly-understood regulation of megakaryocyte-erythrocyte progenitors (MEPs) in hematopoiesis as a model system. We report here that miR-150 modulates lineage fate in MEPs. Using a novel methodology capable of profiling miRNA expression in limiting numbers of primary cells, we identify miR-150 as preferentially expressed in the megakaryocytic lineage. Through gain- and loss-of-function experiments, we demonstrate that miR-150 drives MEP differentiation toward megakaryocytes at the expense of erythroid cells in vitro and in vivo. Moreover, we identify the transcription factor MYB as a critical target of miR-150 in this regulation. These experiments show that miR-150 regulates MEP fate, and thus establish a role for miRNAs in lineage specification of mammalian multi-potent cells.
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    An Erythroid Differentiation Signature Predicts Response to Lenalidomide in Myelodysplastic Syndrome
    (Public Library of Science, 2008) Galili, Naomi; Tamayo, Pablo; Bosco, Jocelyn; Ladd-Acosta, Christine; Raza, Azra; Ebert, Benjamin; Mak, Raymond; Pretz, Jennifer; Tanguturi, Shyam; Stone, Richard; Golub, Todd
    Background: Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS), an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition to the development of leukemia. Patients with an interstitial deletion of Chromosome 5q have a high rate of response to lenalidomide, but most MDS patients lack this deletion. Approximately 25% of patients without 5q deletions also benefit from lenalidomide therapy, but response in these patients cannot be predicted by any currently available diagnostic assays. The aim of this study was to develop a method to predict lenalidomide response in order to avoid unnecessary toxicity in patients unlikely to benefit from treatment. Methods and Findings: Using gene expression profiling, we identified a molecular signature that predicts lenalidomide response. The signature was defined in a set of 16 pretreatment bone marrow aspirates from MDS patients without 5q deletions, and validated in an independent set of 26 samples. The response signature consisted of a cohesive set of erythroid-specific genes with decreased expression in responders, suggesting that a defect in erythroid differentiation underlies lenalidomide response. Consistent with this observation, treatment with lenalidomide promoted erythroid differentiation of primary hematopoietic progenitor cells grown in vitro. Conclusions: These studies indicate that lenalidomide-responsive patients have a defect in erythroid differentiation, and suggest a strategy for a clinical test to predict patients most likely to respond to the drug. The experiments further suggest that the efficacy of lenalidomide, whose mechanism of action in MDS is unknown, may be due to its ability to induce erythroid differentiation.