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3. Src homology 2 domain–containing inositol-5-phosphatase and CCAAT enhancer-binding protein β are targeted by miR-155 in B cells of Eμ-MiR-155 transgenic mice

Author

Costinean, Stefan, Sandhu, Sukhinder K, Pedersen, Irene M, Tili, Esmerina, Trotta, Rossana, Perrotti, Danilo, Ciarlariello, David, Neviani, Paolo, Harb, Jason, Kauffman, Lauren Rachel, Shidham, Aaditya, and Croce, Carlo Maria

Subjects
Hematology, Genetics, Biotechnology, Childhood Leukemia, Pediatric Cancer, Cancer, Rare Diseases, Pediatric, Lymphoma, Aetiology, 2.1 Biological and endogenous factors, Animals, CCAAT-Enhancer-Binding Protein-beta, Cell Transformation, Neoplastic, Down-Regulation, Gene Expression Regulation, Leukemic, Inositol Polyphosphate 5-Phosphatases, Interleukin-6, Lymphoma, B-Cell, Mice, Mice, Transgenic, MicroRNAs, Phosphoric Monoester Hydrolases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cells, B-Lymphoid, Signal Transduction, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology
Abstract

We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

Published
2009

4. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice.

Author

Costinean, Stefan, Sandhu, Sukhinder K, Pedersen, Irene M, Tili, Esmerina, Trotta, Rossana, Perrotti, Danilo, Ciarlariello, David, Neviani, Paolo, Harb, Jason, Kauffman, Lauren Rachel, Shidham, Aaditya, and Croce, Carlo Maria

Subjects
Animals, Mice, Transgenic, Mice, Lymphoma, B-Cell, Cell Transformation, Neoplastic, Phosphoric Monoester Hydrolases, CCAAT-Enhancer-Binding Protein-beta, MicroRNAs, Interleukin-6, Signal Transduction, Down-Regulation, Gene Expression Regulation, Leukemic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cells, B-Lymphoid, Inositol Polyphosphate 5-Phosphatases, Transgenic, Lymphoma, B-Cell, Cell Transformation, Neoplastic, Gene Expression Regulation, Leukemic, Precursor Cells, B-Lymphoid, Immunology, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine
Abstract

We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

Published
2009

5. Supplementary figure legends from Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation

Author

Kapoor, Shivani, primary, Natarajan, Karthika, primary, Baldwin, Patrick R., primary, Doshi, Kshama A., primary, Lapidus, Rena G., primary, Mathias, Trevor J., primary, Scarpa, Mario, primary, Trotta, Rossana, primary, Davila, Eduardo, primary, Kraus, Manfred, primary, Huszar, Dennis, primary, Tron, Adriana E., primary, Perrotti, Danilo, primary, and Baer, Maria R., primary

Published
2023
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6. Figure S5 from Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation

Author

Kapoor, Shivani, primary, Natarajan, Karthika, primary, Baldwin, Patrick R., primary, Doshi, Kshama A., primary, Lapidus, Rena G., primary, Mathias, Trevor J., primary, Scarpa, Mario, primary, Trotta, Rossana, primary, Davila, Eduardo, primary, Kraus, Manfred, primary, Huszar, Dennis, primary, Tron, Adriana E., primary, Perrotti, Danilo, primary, and Baer, Maria R., primary

Published
2023
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7. Supplementary Figure 7 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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8. Supplementary Figure 5 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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9. Supplementary Figure 6 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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10. Supplementary Figure 2 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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11. Supplementary Figure 3 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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12. Table S1 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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13. Data from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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14. Supplementary Figure 1 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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15. Supplementary Figure 4 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, primary, Stramucci, Lorenzo, primary, Ellis, Justin J., primary, Harb, Jason G., primary, Neviani, Paolo, primary, Wang, Shuzhen, primary, Eisfeld, Ann-Kathrin, primary, Walker, Christopher J., primary, Zhang, Bin, primary, Srutova, Klara, primary, Gambacorti-Passerini, Carlo, primary, Pineda, Gabriel, primary, Jamieson, Catriona H. M., primary, Stagno, Fabio, primary, Vigneri, Paolo, primary, Nteliopoulos, Georgios, primary, May, Philippa C., primary, Reid, Alistair G., primary, Garzon, Ramiro, primary, Roy, Denis-Claude, primary, Moutuou, Moutuaata M., primary, Guimond, Martin, primary, Hokland, Peter, primary, Deininger, Michael W., primary, Fitzgerald, Garrett, primary, Harman, Christopher, primary, Dazzi, Francesco, primary, Milojkovic, Dragana, primary, Apperley, Jane F., primary, Marcucci, Guido, primary, Qi, Jianfei, primary, Polakova, Katerina Machova, primary, Zou, Ying, primary, Fan, Xiaoxuan, primary, Baer, Maria R., primary, Calabretta, Bruno, primary, and Perrotti, Danilo, primary

Published
2023
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16. Abstract 3338: Concurrent treatment with Pim kinase inhibitor enhances efficacy of FLT3 inhibitors in AML with FLT3-ITD through GSK-3βactivation and GSK-3β-mediated enhanced proteasomal degradation of c-Myc and Mcl-1

Author

Lee, Jonelle, primary, Scarpa, Mario, additional, Chatterjee, Aditi, additional, Ali, Mooath Mustafa, additional, Singh, Prerna, additional, Kapoor, Shivani, additional, Trotta, Rossana, additional, and Baer, Maria, additional

Published
2022
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23. TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia

Author

Yu, Jianhua, Ershler, Maxim, Yu, Li, Wei, Min, Hackanson, Björn, Yokohama, Akihiko, Mitsui, Takeki, Liu, Chunhui, Mao, Hsiaoyin, Liu, Shujun, Liu, Zhongfa, Trotta, Rossana, Liu, Chang-gong, Liu, Xiuping, Huang, Kun, Visser, Jan, Marcucci, Guido, Plass, Christoph, Belyavsky, Alexander V., and Caligiuri, Michael A.

Published
2009
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26. NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human

Author

Yu, Jianhua, Mitsui, Takeki, Wei, Min, Mao, Hsiaoyin, Butchar, Jonathan P., Shah, Mithun Vinod, Zhang, Jianying, Mishra, Anjali, Alvarez-Breckenridge, Christopher, Liu, Xingluo, Liu, Shujun, Yokohama, Akihiko, Trotta, Rossana, Marcucci, Guido, Benson, Jr., Don M., Loughran, Jr., Thomas P., Tridandapani, Susheela, and Caligiuri, Michael A.

Subjects
T cells -- Health aspects, Gene expression -- Research, Leukemia -- Genetic aspects -- Care and treatment, Health care industry
Abstract

IL-15 may have a role in the development of T cell large granular lymphocyte (T-LGL) or NKT leukemias. However, the mechanisms of action and the identity of the cell subset that undergoes leukemic transformation remain elusive. Here we show that in both mice and humans, NKp46 expression marks a minute population of WT NKT cells with higher activity and potency to become leukemic. Virtually 100% of T-LGL leukemias in IL-15 transgenic mice expressed NKp46, as did a majority of human T-LGL leukemias. The minute [NKp46.sup.+] NKT population, but not the NKp46 NKT population, was selectively expanded by overexpression of endogenous IL-15. Importantly, IL-15 transgenic NKp46 NKT cells did not become [NKp46.sup.+] in vivo, suggesting that [NKp46.sup.+] T-LGL leukemia cells were the malignant counterpart of the minute WT [NKp46.sup.+] NKT population. Mechanistically, [NKp46.sup.+] NKT cells possessed higher responsiveness to IL-15 in vitro and in vivo compared with that of their NKp46 NKT counterparts. Furthermore, interruption of IL-15 signaling using a neutralizing antibody could prevent LGL leukemia in IL-15 transgenic mice. Collectively, our data demonstrate that NKp46 identifies a functionally distinct NKT subset in mice and humans that appears to be directly susceptible to leukemic transformation when IL-15 is overexpressed. Thus, IL-15 signaling and NKp46 maybe useful targets in the treatment of patients with T-LGL or NKT leukemia., Introduction NKT cells are defined as a subset of T cells that share some characteristics with NK cells, particularly expression of the NK1.1 or DX5 antigen in mice and CD56 [...]

Published
2011
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28. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia

Author

Neviani, Paolo, Santhanam, Ramasamy, Oaks, Joshua J., Eiring, Anna M., Notari, Mario, Blaser, Bradley W., Liu, Shujun, Trotta, Rossana, Muthusamy, Natarajan, Gambacorti-Passerini, Carlo, Druker, Brian J., Cortes, Jorge, Marcucci, Guido, Chen, Ching-Shih, Verrills, Nicole M., Roy, Denis C., Caligiuri, Michael A., Bloomfield, Clara D., Byrd, John C., and Perrotti1, Danilo

Subjects
Philadelphia chromosome -- Analysis, Leukemia -- Analysis, Enzyme inhibitors -- Analysis
Abstract

Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive (Ph1-positive) acute lymphocytic leukemia (ALL) are 2 fatal BCR/ABL-driven leukemias against which Abl kinase inhibitors fail to induce a long-term response. [...]

Published
2007

30. Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, Giovannino, primary, Trotta, Rossana, additional, Stramucci, Lorenzo, additional, Ellis, Justin J., additional, Harb, Jason G., additional, Neviani, Paolo, additional, Wang, Shuzhen, additional, Eisfeld, Ann-Kathrin, additional, Walker, Christopher J., additional, Zhang, Bin, additional, Srutova, Klara, additional, Gambacorti-Passerini, Carlo, additional, Pineda, Gabriel, additional, Jamieson, Catriona H. M., additional, Stagno, Fabio, additional, Vigneri, Paolo, additional, Nteliopoulos, Georgios, additional, May, Philippa C., additional, Reid, Alistair G., additional, Garzon, Ramiro, additional, Roy, Denis-Claude, additional, Moutuou, Moutuaata M., additional, Guimond, Martin, additional, Hokland, Peter, additional, Deininger, Michael W., additional, Fitzgerald, Garrett, additional, Harman, Christopher, additional, Dazzi, Francesco, additional, Milojkovic, Dragana, additional, Apperley, Jane F., additional, Marcucci, Guido, additional, Qi, Jianfei, additional, Polakova, Katerina Machova, additional, Zou, Ying, additional, Fan, Xiaoxuan, additional, Baer, Maria R., additional, Calabretta, Bruno, additional, and Perrotti, Danilo, additional

Published
2020
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31. A 14q32.31 Genomic-Imprinted DLK1-DIO3 microrna promotes Leukemogenesis By Inducing Stem Cell Quiescence and Inhibiting NK Cell Anti-Cancer Immunity

Author

Silvestri, Giovannino, primary, Trotta, Rossana, additional, Stramucci, Lorenzo, additional, Wang, Shuzhen, additional, Eisfeld, Ann-Kathrin, additional, Zhang, Bin, additional, Srutova, Klara, additional, Pineda, Gabriel, additional, Jamieson, Catriona, additional, Stagno, Fabio, additional, Vigneri, Paolo, additional, Nteliopoulos, Georgios, additional, Guimond, Martin, additional, Hokland, Peter, additional, Deininger, Michael W., additional, Dazzi, Francesco, additional, Milojkovic, Dragana, additional, Apperley, Jane, additional, Marcucci, Guido, additional, Fan, Xiaoxuan, additional, Baer, Maria R., additional, Calabretta, Bruno, additional, and Perrotti, Danilo, additional

Published
2019
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32. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein

Author

Neviani, Paolo, Santhanam, Ramasamy, Trotta, Rossana, Notari, Mario, Blaser, Bradley W., Liu, Shujun, Mao, Hsiaoyin, Chang, Ji Suk, Galietta, Annamaria, Uttam, Ashwin, Roy, Denis C., Valtieri, Mauro, Bruner-Klisovic, Rebecca, Caligiuri, Michael A., Bloomfield, Clara D., Marcucci, Guido, and Perrotti, Danilo

Published
2005
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35. The 14q32.31DLK1-DIO3 MIR300 tumor suppressorpromotes leukemogenesis by inducing cancer stem cell quiescence and inhibiting NK cell anti-cancer immunity

Author

Silvestri, Giovannino, primary, Trotta, Rossana, additional, Stramucci, Lorenzo, additional, Ellis, Justin J., additional, Harb, Jason G., additional, Neviani, Paolo, additional, Wang, Shuzhen, additional, Eisfeld, Ann-Kathrin, additional, Walker, Christopher, additional, Zhang, Bin, additional, Srutova, Klara, additional, Gambacorti-Passerini, Carlo, additional, Pineda, Gabriel, additional, Jamieson, Catriona H. M., additional, Stagno, Fabio, additional, Vigneri, Paolo, additional, Nteliopoulos, Georgios, additional, May, Philippa, additional, Reid, Alistair, additional, Garzon, Ramiro, additional, Roy, Denis C., additional, Moutuou, Moutua-Mohamed, additional, Guimond, Martin, additional, Hokland, Peter, additional, Deininger, Michael, additional, Fitzgerald, Garrett, additional, Harman, Christopher, additional, Dazzi, Francesco, additional, Milojkovic, Dragana, additional, Apperley, Jane F., additional, Marcucci, Guido, additional, Qi, Janfei, additional, Machova-Polakova, Katerina, additional, Zou, Ying, additional, Fan, Xiaoxuan, additional, Baer, Maria R., additional, Calabretta, Bruno, additional, and Perrotti, Danilo, additional

Published
2019
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38. BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia

Author

Srutova, Klara, primary, Curik, Nikola, additional, Burda, Pavel, additional, Savvulidi, Filipp, additional, Silvestri, Giovannino, additional, Trotta, Rossana, additional, Klamova, Hana, additional, Pecherkova, Pavla, additional, Sovova, Zofie, additional, Koblihova, Jitka, additional, Stopka, Tomas, additional, Perrotti, Danilo, additional, and Polakova, Katerina Machova, additional

Published
2018
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40. Abstract 1134: The tumor suppressor activity of miR-300 is detrimental for leukemia development but required for leukemia stem cell maintenance

Author

Silvestri, Giovannino, primary, Stramucci, Lorenzo, additional, Ellis, Justin, additional, Harb, Jason, additional, Neviani, Paolo, additional, Zhang, Bin, additional, Srutova, Klara, additional, Pineda, Gabriel, additional, Jamieson, Catriona, additional, Calabretta, Bruno, additional, Stagno, Fabio, additional, Vigneri, Paolo, additional, Nteliopoulos, Georgios, additional, May, Philippa, additional, Reid, Alistar, additional, Garzon, Ramiro, additional, Roy, Denis-Claude, additional, Guimond, Martin, additional, Hokland, Peter, additional, Deininger, Michael, additional, Fitzgerald, Garrett, additional, Harman, Chris, additional, Dazzi, Francesco, additional, Milojkovic, Dragana, additional, Apperley, Jane, additional, Marcucci, Guido, additional, Qi, Jianfei, additional, Machova-Polakova, Katerina, additional, Fan, Xiaoxuan, additional, Baer, Maria, additional, Trotta, Rossana, additional, and Perrotti, Danilo, additional

Published
2018
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41. Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation

Author

Kapoor, Shivani, primary, Natarajan, Karthika, additional, Baldwin, Patrick R., additional, Doshi, Kshama A., additional, Lapidus, Rena G., additional, Mathias, Trevor J., additional, Scarpa, Mario, additional, Trotta, Rossana, additional, Davila, Eduardo, additional, Kraus, Manfred, additional, Huszar, Dennis, additional, Tron, Adriana E., additional, Perrotti, Danilo, additional, and Baer, Maria R., additional

Published
2018
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43. Potential Targeting Ph+ Acute Lymphoblastic Leukemia Stem and Progenitor Cells By Modulating the CIP2A-SET-SETBP1 -Mediated Suppression of PP2A Activity

Author

Yu, Justine, primary, Silvestri, Giovannino, additional, Stramucci, Lorenzo, additional, Sanada, Masashi, additional, Yamaguchi, Tomoyuki, additional, Du, Yang, additional, Westermarck, Jukka, additional, Caligiuri, Michael A., additional, Garzon, Ramiro, additional, Milojkovic, Dragana, additional, Apperley, Jane F., additional, Roy, Denis-Claude, additional, Marcucci, Guido, additional, Calabretta, Bruno, additional, Baer, Maria R., additional, Trotta, Rossana, additional, and Perrotti, Danilo, additional

Published
2016
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44. Concurrent Inhibition of Pim-1 and FLT3 Kinases in FLT3-ITD Acute Myeloid Leukemia Post-Translationally Downregulates the Anti-Apoptotic Protein Mcl-1 through Downregulation of the Mcl-1 Deubiquitinase USP9X

Author

Baldwin, Patrick R., primary, Kapoor, Shivani, additional, Natarajan, Karthika, additional, Trotta, Rossana, additional, Tron, Adriana, additional, Huszar, Dennis, additional, Davila, Eduardo, additional, Perrotti, Danilo, additional, and Baer, Maria R., additional

Published
2016
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45. AHR prevents human IL-1R1hi ILC3 differentiation to natural killer cells

Author

Hughes, Tiffany, Briercheck, Edward L., Freud, Aharon G., Trotta, Rossana, McClory, Susan, Scoville, Steven D., Keller, Karen, Deng, Youcai, Cole, Jordan, Harrison, Nicholas, Mao, Charlene, Zhang, Jianying, Benson, Don M., Yu, Jianhua, and Caligiuri, Michael A.

Subjects
Killer Cells, Natural, Receptors, Interleukin-1 Type I, Receptors, Aryl Hydrocarbon, Interleukins, Palatine Tonsil, Basic Helix-Loop-Helix Transcription Factors, Humans, Cell Differentiation, Cell Lineage, Lymphocytes, Article, CD56 Antigen, Cells, Cultured
Abstract

Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called "stage 3" developmental intermediate minimally characterized by a CD34(-)CD117(+)CD94(-) immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that include interleukin-1 receptor (IL-1R1)-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1(hi) human ILC3s to CD56(bright)CD94(+) interferon (IFN)-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1(hi) ILC3s from differentiating into NK cells.

Published
2014

46. Abstract 951: Role of the MSC-derived exosomal and endogenous JAK2-SET/PP2A-β-catenin-modulator miR-300 in leukemic stem/progenitor proliferation and survival in CML

Author

Trotta, Rossana, primary, Silvestri, Giovannino, additional, Stramucci, Lorenzo, additional, Ellis, Justin J., additional, Yu, Justine, additional, Harb, Jason J., additional, Neviani, Paolo, additional, Marcucci, Guido, additional, Srutova, Klara, additional, Machova, Polakova K., additional, Roy, Denis-Claude, additional, Hokland, Peter, additional, Deininger, Michael, additional, Bhatia, Ravi, additional, Gambacorti-Passerini, Carlo, additional, Milojkovic, Dragana, additional, Reid, Alistair, additional, Apperley, Jane, additional, Livak, Ferenc, additional, Qi, Jianfei, additional, Baer, Maria R., additional, and Perrotti, Danilo, additional

Published
2016
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49. Role of the MSC-Derived Exosomal and Endogenous JAK2-SET/PP2A-Beta Catenin-Modulator Mir-300 in Leukemic Stem/Progenitor Proliferation and Survival in CML

Author

Silvestri, Giovannino, primary, Stramucci, Lorenzo, additional, Ellis, Justin, additional, Yu, Justine, additional, Harb, Jason, additional, Neviani, Paolo, additional, Marcucci, Guido, additional, Srutova, Klara, additional, Machova Polakova, Katerina, additional, Roy, Denis-Claude, additional, Hokland, Peter, additional, Deininger, Michael W., additional, Bhatia, Ravi, additional, Gambacorti-Passerini, Carlo, additional, Milojkovic, Dragana, additional, Reid, Alistair G, additional, Apperley, Jane F., additional, Livak, Ferenc, additional, Baer, Maria R., additional, Trotta, Rossana, additional, and Perrotti, Danilo, additional

Published
2015
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50. Axl/Gas6 pathway participates in human natural killer cell development by positively regulating FLT3 activation

Author

Park, Il-Kyoo, Trotta, Rossana, Yu, Jianhua, and Caligiuri, Michael A.

Subjects
Interleukin-15, Recombinant Fusion Proteins, Receptor Protein-Tyrosine Kinases, hemic and immune systems, Antigens, CD34, Cell Differentiation, Hematopoietic Stem Cells, Lymphocyte Activation, Axl Receptor Tyrosine Kinase, Article, Immunoglobulin Fc Fragments, Interleukin-2 Receptor beta Subunit, Killer Cells, Natural, fms-Like Tyrosine Kinase 3, Proto-Oncogene Proteins, embryonic structures, Humans, Intercellular Signaling Peptides and Proteins, Phosphorylation, Cells, Cultured, Interleukin Receptor Common gamma Subunit, Protein Binding, Signal Transduction
Abstract

Activation of the fibromyalgia syndrome-like tyrosine kinase 3 (FLT3) by its ligand, FLT3 ligand (FL), strongly augments the development of natural killer (NK) cells from human CD34⁺ hematopoietic progenitor cells (HPCs) in the presence of IL-15, compared with NK-cell development in the presence of IL-15 alone. In this study, we observed that blocking the receptor tyrosine kinase Axl/Gas6 pathway with a soluble Axl-IgG1 Fc fusion protein (Axl-Fc) in the presence of FL significantly diminished the absolute number of CD3⁻ CD56⁺ NK cells derived from human CD34⁺ HPCs. Axl-Fc reduced the expression levels of the IL-2/15 receptor β chain (CD122) and γ chain (CD132) induced by activation of FLT3 and consequently reduced the frequency of NK precursor cells responding to IL-15. Furthermore, Axl-Fc diminished FL-induced FLT3 phosphorylation and impeded the physical interaction between Axl and FLT3 in CD34⁺ HPCs. Collectively, our data suggest that the Axl/Gas6 pathway contributes to normal human NK-cell development at least in part via its positive regulatory effect on FLT3 signaling in CD34⁺ HPCs.

Published
2013

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