Hyaluronan oligomers sensitize chronic myeloid leukemia cell lines to the effect of Imatinib

LOMBARDIA S.; MASCARÓ M; HAJOS S; DIAZ M; PIBUEL M; PAPADEMETRIO D; ALVAREZ ELIDA

GLYCOBIOLOGY

OXFORD UNIV PRESS INC

Lugar: Oxford; Año: 2016 vol. 2016 p. 343 - 352

0959-6658

Chronic myeloid leukemia is a myeloproliferative syndrome characterized by the presence of thePhiladelphia chromosome (Ph), generated by a reciprocal translocation occurring between chromosomes9 and 22 [t(9;22)(q34;q11)]. As a consequence, a fusion gene (bcr-abl) encoding a constitutivelyactive kinase is generated. The first-line treatment consists on BCR-ABL inhibitors such as Imatinib,Nilotinib and Dasatinib. Nevertheless, such treatment may lead to the selection of resistant cells.Therefore, finding molecules that enhance the anti-proliferative effect of first-line drugs is of value.Hyaluronan oligomers (oHA) are known to be able to sensitize several tumor cells to chemotherapy.We have previously demonstrated that oHA can revert Vincristine resistance in mouse lymphomaand human leukemia cell lines. However, little is known about the role of oHA in hematologicalmalignancies. The aim of this work was to determine whether oHA are able to modulate the antiproliferativeeffect of Imatinib in chronic myeloid leukemia (CML) cell lines. The effect on apoptosisand senescence as well as the involvement of signaling pathways were also evaluated. For thispurpose, the human CML cell lines K562 and Kv562 (resistant) were used. We demonstrated thatoHA sensitized both cell lines to the anti-proliferative effect of Imatinib increasing apoptosis andsenescence. Moreover, this effect would be accomplished through the down-regulation of thePI3K signaling pathway. These findings highlight the potential of oHA when used as a co-adjuvanttherapy for chronic myeloid leukemia.