Possible involvement of tyrosine kinase inhibitors on the expression of CXCR4 in chronic myeloid leukemia

Thiago Fujita, Glauco Vitiello, Marla Karine Amarante, Carlos Oliveira, Bruna Hirata, Julie Oda, Luis Turkowski, Maria Watanabe


Purpose: Chronic myeloid leukemia (CML) treatment has improved significantly in the last decade with the introduction of tyrosine kinase inhibitors (TKIs), which target BCR/ABL oncoprotein. However, a large proportion of patients develop resistance to this treatment protocol, with frequent relapse cases. CXCR4 up-regulation in leukemic cells induced by TKIs has been reported as a mechanism of chemoresistance by promoting migration of these cells to bone marrow, where they receive pro-survival signals and persist as quiescent cells. In the present study, we investigated the possible influence of treatment on the expression of CXCR4 and CXCL12 in peripheral blood cells of CML patients.

Methods: Relative expressions (RE) were calculated from mRNA obtained from leukocytes of 21 patients in chronic phase, under treatment, and 54 healthy individuals, used as controls.

Results: CXCR4 expression was increased in CML patients compared to controls (RE: 1.931; p = 0.006). In CML patients, CXCR4 and CXCL12 expressions were correlated (r = 0.631; p = 0.002), and no differences in the expression of these genes were observed among different treatment protocols. However, CXCR4 expression was positively correlated with imatinib treatment period duration of treatment (r = 0.56; p = 0.02).

Conclusion: This data has pointed peripheral blood CXCR4 expression as a possible marker for treatment monitoring, which may be useful to predict which patients would be benefit from newly developed treatments targeting CXCR4 and BCR/ABL concomitantly.


Chronic Myeloid Leukemia; Tyrosine Kinase Inhibitors; CXCL12; CXCR4

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DOI: http://dx.doi.org/10.14319/ijcto.34.5

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