The tyrosine kinase inhibitors (TKIs) represent the successful molecular therapy for patients with chronic myeloid leukemia (CML), targeting the Bcr-Abl oncogenic product. However, this disease may remain not curable for the presence of residual refractory cells, persisting during the history of the disease treatment. Several mechanisms have been associated with resistance to TKIs, including the presence of rare quiescent leukemic stem cells, less susceptible to TKIs. Moreover, Bcr-Abl activates additional downstream pathways involved in the apoptotic and proliferation control of CML cells, such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5 pathways, potentially contributing to CML TKIs drug resistance. Therefore, in this study we aimed to investigate, at the protein level, proliferative and apoptotic signal transduction pathways (STP) in CML CD34+ cells, as compared to normal CD34+ cells, in order to identify additional aberrant signals, potentially therapeutic targetable. CD34+ cells were
Proteomic signature of CD34+ cells from chronic myeloid leukemia patients / Ricciardi, Maria Rosaria; V., Salvestrini; Licchetta, Roberto; Mirabilii, Simone; M. T., Petrucci; L., Rossi; Allegretti, Matteo; S., Salati; F., Castagnetti; G., Rosti; G., Alimena; R., Manfredini; R. M., Lemoli; Tafuri, Agostino. - In: BLOOD. - ISSN 0006-4971. - ELETTRONICO. - 120:(2012). (Intervento presentato al convegno ASH Annual Meeting tenutosi a Atlanta, Georgia, USA nel 8-11/12/2012).
Proteomic signature of CD34+ cells from chronic myeloid leukemia patients
RICCIARDI, Maria Rosaria;LICCHETTA, ROBERTO;MIRABILII, SIMONE;ALLEGRETTI, MATTEO;TAFURI, Agostino
2012
Abstract
The tyrosine kinase inhibitors (TKIs) represent the successful molecular therapy for patients with chronic myeloid leukemia (CML), targeting the Bcr-Abl oncogenic product. However, this disease may remain not curable for the presence of residual refractory cells, persisting during the history of the disease treatment. Several mechanisms have been associated with resistance to TKIs, including the presence of rare quiescent leukemic stem cells, less susceptible to TKIs. Moreover, Bcr-Abl activates additional downstream pathways involved in the apoptotic and proliferation control of CML cells, such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5 pathways, potentially contributing to CML TKIs drug resistance. Therefore, in this study we aimed to investigate, at the protein level, proliferative and apoptotic signal transduction pathways (STP) in CML CD34+ cells, as compared to normal CD34+ cells, in order to identify additional aberrant signals, potentially therapeutic targetable. CD34+ cells wereI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
