title: Phosphorylation of spleen tyrosine kinase at tyrosine 348 (pSyk³⁴⁸) may be a marker of advanced phase of Chronic Myeloid Leukemia (CML).
abstract: We investigated Syk as a potential marker of CML progression. We observed a significant over-expression of Syk mRNA and constitutive phosphorylation of Syk Y348 in blast cells from six AP or BP-CML, but not in 15 CML in chronic phase. We could follow in vivo the recurrence of pSyk(348) throughout blast cell escape, despite observing storage of dasatinib in blast cells. A combination of dasatinib and R406 did not improve therapeutic efficacy in vitro. Our results strongly suggest that Syk activation could be a relevant biomarker of disease progression and dasatinib resistance but is probably not a molecular target.
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bourgne
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Janel
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Berger
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Rapatel
authors.affiliation: Hématologie Clinique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.affiliation: Hématologie Clinique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hermet
authors.affiliation: Hématologie et Médecine Interne, CHU Brabois, Rue Morvan, 54500 Vandoeuvre-lès-Nancy, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Guerci
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lioret
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Briançon
authors.affiliation: Laboratoire Microorganismes, Génome et Environnement (LMGE) - UMR CNRS 6023, Université Blaise Pascal, UFR Sciences et Technologies, 24, avenue des Landais, BP 80026, 63171 Aubière Cedex, France.
authors.forename: Mahchid
authors.initials: M
authors.lastname: Bamdad
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boiret-Dupré
authors.affiliation: Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France. Electronic address: mberger@chu-clermontferrand.fr.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Berger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor; D001752:Blast Crisis; D002648:Child; D002908:Chronic Disease; D000069439:Dasatinib; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000494:pharmacology; D010766:Phosphorylation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000072377:Syk Kinase; D013844:Thiazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C510788:N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine; D010078:Oxazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D012333:RNA, Messenger; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D000069439:Dasatinib
keywords: Chronic Myeloid Leukemia (CML); Dasatinib; Flow cytometry; Spleen tyrosine kinase (Syk); pSyk(348)