51. High BCR::ABL1 Expression Defines CD34+ Cells with Significant Alterations in Signal Transduction, Short-Proliferative Potential and Self-Renewal Ability
- Author
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Massimino,Michele, Stella,Stefania, Tirrò,Elena, Pennisi,Maria Stella, Stagno,Fabio, Vitale,Silvia Rita, Romano,Chiara, Tomarchio,Cristina, Parrinello,Nunziatina Laura, Manzella,Livia, Di Raimondo,Francesco, Vigneri,Paolo, Massimino,Michele, Stella,Stefania, Tirrò,Elena, Pennisi,Maria Stella, Stagno,Fabio, Vitale,Silvia Rita, Romano,Chiara, Tomarchio,Cristina, Parrinello,Nunziatina Laura, Manzella,Livia, Di Raimondo,Francesco, and Vigneri,Paolo
- Abstract
Michele Massimino,1,2,* Stefania Stella,2,3,* Elena Tirrò,2,3 Maria Stella Pennisi,2,3 Fabio Stagno,4 Silvia Rita Vitale,2,3 Chiara Romano,2,5 Cristina Tomarchio,2,3 Nunziatina Laura Parrinello,4 Livia Manzella,2,3 Francesco Di Raimondo,4 Paolo Vigneri2,3,6 1Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy; 2Center of Experimental Oncology and Hematology, A.O.U. Policlinico âG. Rodolico-S. Marcoâ, Catania, Italy; 3Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; 4Division of Hematology, A.O.U. Policlinico âG. Rodolico-S. Marcoâ, Catania, Italy; 5Department of Medical, Surgical Sciences and Advanced Technologies âG.F. Ingrassiaâ, Anatomic Pathology, University of Catania, Catania, Italy; 6Humanitas Istituto Clinico Catanese, University Oncology Department, Catania, Italy*These authors contributed equally to this workCorrespondence: Michele Massimino, A.U.O. Policlinico G. Rodolico S. Marco, Via Santa Sofia 78, Catania, 95123, Italy, Tel +39-95-3781952, Fax +39-95-3781949, Email michedot@yahoo.itPurpose: Chronic Myeloid Leukemia (CML) is a clonal disorder of the hematopoietic stem cell caused by expression of the BCR::ABL1 oncoprotein. High BCR::ABL1 levels have been associated to proliferative advantage of leukemic cells, blast crisis progression and tyrosine kinase inhibitors (TKIs) inefficacy. We have previously shown that high BCR::ABL1/GUSIS transcripts measured at diagnosis are associated with inferior responses to standard dose Imatinib (IM). However, the mechanisms underlying the higher rates of disease progression and development of TKIs resistance dependent on elevated BCR::ABL1 levels remain unclear.Methods: Leukemic cells were collected from CML patients showing, at diagnosis, high or low BCR::ABL1/GUSIS. BCR::ABL1 expression levels were measured using real-time PCR. Short-term culture and long-term culture-initiating cells assays were
- Published
- 2023