Longitudinal studies of SRC family kinases in imatinib- and dasatinib-resistant chronic myelogenous leukemia patients.
This report aims to more accurately define the frequency of the involvement of SRC Family Kinases (SFKs) in imatinib- and dasatinib-resistant CML patients. Clinical samples were analysed during in vivo treatment. We confirmed the high frequency of SFKs involvement in Tyrosine kinase inhibitor-resistant CML (52% of the cases) and even further in progressive disease and blast crises (60% of the cases). The SFKs deregulation is also observed in patients harboring BCR-ABL mutations. In T315I and F317L mutated patients, CML-resistance appears to be promoted by SFKs kinase protein reactivation once the BCR-ABL mutated clone has decreased on Omacetaxine.
Hayette
Sandrine
S
Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Laboratory for Molecular Biology and UMR5239 CNRS, Pierre-Bénite, France. sandrine.hayette@chu-lyon.fr
Chabane
Kaddour
K
Michallet
Mauricette
M
Michallat
Estelle
E
Cony-Makhoul
Pascale
P
Salesse
Stéphanie
S
Maguer-Satta
Véronique
V
Magaud
Jean-Pierre
JP
Nicolini
Franck E
FE
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides; D045744:Cell Line, Tumor; D017931:DNA Primers; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008137:Longitudinal Studies; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D019061:src-Family Kinases / Q000378:metabolism*
D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D019061:src-Family Kinases; D000069439:Dasatinib