Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia

Daniela Cilloni; Sonia Carturan; Enrico Bracco; Valentina Campia; Valentina Rosso; Davide Torti; Chiara Calabrese; Valentina Gaidano; Pimjai Niparuck; Alessandra Favole; Elisabetta Signorino; Ilaria Iacobucci; Annalisa Morano; Luciana De Luca; Pellegrino Musto; Francesco Frassoni; Giuseppe Saglio

doi:10.1016/j.leukres.2013.01.014

Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia

Daniela Cilloni, Sonia Carturan, Enrico Bracco, Valentina Campia, Valentina Rosso, Davide Torti, Chiara Calabrese, Valentina Gaidano, Pimjai Niparuck, Alessandra Favole, Elisabetta Signorino, Ilaria Iacobucci, Annalisa Morano, Luciana De Luca, Pellegrino Musto, Francesco Frassoni, Giuseppe Saglio

Research output: Contribution to journal › Article › peer-review

Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal disorder sharing features of myelodysplastic syndromes and chronic myeloproliferative neoplasms. Although rare chromosomal aberrations and point mutations are reported in CMML, the molecular defects underlying CMML are largely unknown. ROS1 encodes a tyrosine kinase that is abnormally expressed and translocated in brain and lung cancers. In this study we show that ROS1 is abnormally activated in the CD34+ compartment of approximately 70% of CMML patients resulting in the activation of the Erk/Akt pathways through the Grb2/SOS complex thus revealing a central oncogenic role for ROS1 in CMML which might represent a molecular target.

Original language	English
Pages (from-to)	520-530
Number of pages	11
Journal	Leukemia Research
Volume	37
Issue number	5
DOIs	https://doi.org/10.1016/j.leukres.2013.01.014
Publication status	Published - May 2013

Keywords

Chronic myeloproliferative neoplasms
CMML
Molecular target
Proliferation
ROS1
Tyrosine kinase

ASJC Scopus subject areas

Cancer Research
Hematology
Oncology

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Cilloni, D., Carturan, S., Bracco, E., Campia, V., Rosso, V., Torti, D., Calabrese, C., Gaidano, V., Niparuck, P., Favole, A., Signorino, E., Iacobucci, I., Morano, A., De Luca, L., Musto, P., Frassoni, F., & Saglio, G. (2013). Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia. Leukemia Research, 37(5), 520-530. https://doi.org/10.1016/j.leukres.2013.01.014

Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia. / Cilloni, Daniela; Carturan, Sonia; Bracco, Enrico; Campia, Valentina; Rosso, Valentina; Torti, Davide; Calabrese, Chiara; Gaidano, Valentina; Niparuck, Pimjai; Favole, Alessandra; Signorino, Elisabetta; Iacobucci, Ilaria; Morano, Annalisa; De Luca, Luciana; Musto, Pellegrino; Frassoni, Francesco; Saglio, Giuseppe.

In: Leukemia Research, Vol. 37, No. 5, 05.2013, p. 520-530.

Research output: Contribution to journal › Article › peer-review

Cilloni, D, Carturan, S, Bracco, E, Campia, V, Rosso, V, Torti, D, Calabrese, C, Gaidano, V, Niparuck, P, Favole, A, Signorino, E, Iacobucci, I, Morano, A, De Luca, L, Musto, P, Frassoni, F & Saglio, G 2013, 'Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia', Leukemia Research, vol. 37, no. 5, pp. 520-530. https://doi.org/10.1016/j.leukres.2013.01.014

Cilloni, Daniela ; Carturan, Sonia ; Bracco, Enrico ; Campia, Valentina ; Rosso, Valentina ; Torti, Davide ; Calabrese, Chiara ; Gaidano, Valentina ; Niparuck, Pimjai ; Favole, Alessandra ; Signorino, Elisabetta ; Iacobucci, Ilaria ; Morano, Annalisa ; De Luca, Luciana ; Musto, Pellegrino ; Frassoni, Francesco ; Saglio, Giuseppe. / Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia. In: Leukemia Research. 2013 ; Vol. 37, No. 5. pp. 520-530.

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AB - Chronic myelomonocytic leukemia (CMML) is a clonal disorder sharing features of myelodysplastic syndromes and chronic myeloproliferative neoplasms. Although rare chromosomal aberrations and point mutations are reported in CMML, the molecular defects underlying CMML are largely unknown. ROS1 encodes a tyrosine kinase that is abnormally expressed and translocated in brain and lung cancers. In this study we show that ROS1 is abnormally activated in the CD34+ compartment of approximately 70% of CMML patients resulting in the activation of the Erk/Akt pathways through the Grb2/SOS complex thus revealing a central oncogenic role for ROS1 in CMML which might represent a molecular target.

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