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17-06-2015 | Chronic myeloid leukaemia | News | Article

CML cell IL-6 production induces progenitor cell changes

medwireNews: Chronic myeloid leukaemia (CML) cells alter the function of healthy haematopoietic progenitor cells via interleukin (IL)-6, suggest study findings published in Cancer Cell.

Moreover, blocking IL-6 prevented the CML cells from inducing changes in the differentiation of normal cells, report Daniel Tenen, from National University of Singapore, and co-authors.

“These findings implicate a drug-targetable mechanism that could account for significant malignancy-related abnormalities in CML”, they believe.

The researchers developed a double transgenic mouse model of chronic phase CML by expression of the BCR–ABL oncogenic fusion under the control of a tetracycline-regulated enhancer of the murine stem cell leukaemia gene.

The transgenic mice experienced an increase in myeloid cells and a reduction of lymphoid cells compared with control mice, and this occurred with both transformed cells, expressing BCR–ABL, and normal cells.

Marrow samples taken from mice 4 weeks after CML induction revealed significant increases in numbers of progenitor cells, but not stem cells, and further analysis indicated that leukaemic environment altered the lymphopoiesis capacity of progenitor but not stem cells.

The researchers also discovered that leukaemic progenitor cells produced the inflammatory cytokine IL-6; exposure to the tyrosine kinase inhibitor imatinib reduced IL-6 levels, suggesting that the “leukemic bystander effects are dependent on tyrosine kinase activity, can drive IL-6 production, and are likely reversible”, they write.

When IL-6 was blocked using an antibody, the CML mice did not experience myeloid expansion or splenomegaly until treatment was discontinued. Moreover, this effect was repeated in human cultures of bone marrow cells taken from chronic-phase CML patients.

“Given the contribution of IL-6 to a wide range of human inflammatory diseases, clinically effective strategies have already been developed for its neutralization”, Tenen et al observe.

“Our results suggest that this approach might be an effective therapy in drug-resistant CML or other leukemias with pro-inflammatory signatures, specifically, those in which the leukemic cells are also found to have an adverse impact on untransformed bystander hematopoietic cells.”

By Lynda Williams

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015