Biomaterial Database

Mer receptor tyrosine kinase is a therapeutic target in pre-B-cell acute lymphoblastic leukemia. 2013

Rachel M A Linger, and Alisa B Lee-Sherick, and Deborah DeRyckere, and Rebecca A Cohen, and Kristen M Jacobsen, and Amy McGranahan, and Luis N Brandão, and Amanda Winges, and Kelly K Sawczyn, and Xiayuan Liang, and Amy K Keating, and Aik Choon Tan, and H Shelton Earp, and Douglas K Graham

Department of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplantation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 85%. However, alterations to treatment strategies using available drugs are unlikely to provide significant improvement in survival or decrease therapy-associated toxicities. Here, we report ectopic expression of the Mer receptor tyrosine kinase in pre-B-cell ALL (B-ALL) cell lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines decreased activation of AKT and MAPKs and led to transcriptional changes, including decreased expression of antiapoptotic PRKCB gene and increase in proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted chemosensitization, decreased colony-forming potential in clonogenic assays, and delayed disease onset in a mouse xenograft model of leukemia. Our results identify Mer as a potential therapeutic target in B-ALL and suggest that inhibitors of Mer may potentiate lymphoblast killing when used in combination with chemotherapy. This strategy could reduce minimal residual disease and/or allow for chemotherapy dose reduction, thereby leading to improved event-free survival and reduced therapy-associated toxicity for patients with B-ALL. Additionally, Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications.

UI	MeSH Term	Description	Entries
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011518	Proto-Oncogene Proteins	Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.	Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076202	c-Mer Tyrosine Kinase	A receptor tyrosine kinase that transduces signals from EXTRACELLULAR MATRIX to the CYTOPLASM by binding ligands such as GALECTIN 3. It regulates many physiologic processes that include cell survival, migration, differentiation, and PHAGOCYTOSIS of apoptotic cells and ROD PHOTORECEPTORS in the RETINAL PIGMENT EPITHELIUM. Mutations in the MERTK gene are associated with type 38 RETINITIS PIGMENTOSA; it also plays a critical role as an inhibitor of TOLL-LIKE RECEPTORS signaling.	MERTK,c-Mer Proto-Oncogene Tyrosine Kinase,Kinase, c-Mer Tyrosine,Tyrosine Kinase, c-Mer,c Mer Proto Oncogene Tyrosine Kinase,c Mer Tyrosine Kinase
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D015452	Precursor B-Cell Lymphoblastic Leukemia-Lymphoma	A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.	Leukemia, Pre-B-Cell,Pre-B-Cell Leukemia,Pre B-ALL,Pre-B ALL,Precursor B-Cell Lymphoblastic Leukemia,Precursor B-Cell Lymphoblastic Lymphoma,Leukemia, Pre B Cell,Leukemias, Pre-B-Cell,Pre B ALL,Pre B Cell Leukemia,Pre-B-Cell Leukemias,Precursor B Cell Lymphoblastic Leukemia,Precursor B Cell Lymphoblastic Leukemia Lymphoma,Precursor B Cell Lymphoblastic Lymphoma
D015973	Gene Expression Regulation, Leukemic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.	Leukemic Gene Expression Regulation,Regulation of Gene Expression, Leukemic,Regulation, Gene Expression, Leukemic
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines