Phosphorylation of spleen tyrosine kinase at tyrosine 348 (pSyk348) may be a marker of advanced phase of Chronic Myeloid Leukemia (CML)

• Over-expression of Syk mRNA in blast cells from BP-CML but not in CP-CML.
• Constitutive phosphorylation of Syk Y348 in blast cells from BP-CML but not in CP-CML.
• Recurrence of pSyk348 throughout blast cell escape, despite storage of dasatinib.
• Combination of dasatinib and R406 did not improve therapeutic efficacy in vitro.
• Syk activation could be a relevant biomarker of CML disease progression.

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 pSyk348 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.