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Assessment of bone marrow lymphocytic status during tyrosine kinase inhibitor therapy and its relation to therapy response in chronic myeloid leukaemia
Univ Helsinki, Dept Hematol, Hematol Res Unit Helsinki, Haartmaninkatu 8,POB 700, FIN-00290 Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Haartmaninkatu 8,POB 700, FIN-00290 Helsinki, Finland..
Univ Helsinki, Dept Hematol, Hematol Res Unit Helsinki, Haartmaninkatu 8,POB 700, FIN-00290 Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Haartmaninkatu 8,POB 700, FIN-00290 Helsinki, Finland..
Univ Helsinki, Dept Hematol, Hematol Res Unit Helsinki, Haartmaninkatu 8,POB 700, FIN-00290 Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Haartmaninkatu 8,POB 700, FIN-00290 Helsinki, Finland..
Univ Helsinki, Inst Clin Med, Helsinki, Finland..
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2016 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 142, no 5, 1041-1050 p.Article in journal (Refereed) PublishedText
Abstract [en]

Tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukaemia have been reported to induce immunomodulatory effects. We aimed to assess peripheral blood (PB) and bone marrow (BM) lymphocyte status at the diagnosis and during different TKI therapies and correlate it with treatment responses. BM and PB samples were acquired from 105 first-line TKI-treated patients. Relative number of BM lymphocytes was evaluated from MGG-stained BM aspirates, and immunophenotypic analyses were performed with multicolour flow cytometry. Early 3-month expansion of BM lymphocytes was found during all different TKIs (imatinib n = 71, 20 %; dasatinib n = 25, 21 %; nilotinib n = 9, 22 %; healthy controls n = 14, 12 %, p < 0.0001). Increased PB lymphocyte count was only observed during dasatinib therapy. The BM lymphocyte expansion was associated with early molecular response; patients with 3-month BCR-ABL1 < 10 % showed higher lymphocyte counts than patients with BCR-ABL1 > 10 % (23 vs. 17 %, p < 0.05). Detailed phenotypic analysis showed that BM lymphocyte expansion consisted of various lymphocyte subclasses, but especially the proportion of CD19+ B cells and CD3negCD16/56+ NK cells increased from diagnostic values. During dasatinib treatment, the lymphocyte balance in both BM and PB was shifted more to cytotoxic direction (increased CD8+CD57+ and CD8+HLA-DR+ cells, and low T regulatory cells), whereas no major immunophenotypic differences were observed between imatinib and nilotinib patients. Early BM lymphocytosis occurs with all current first-line TKIs and is associated with better treatment responses. PB and BM immunoprofile during dasatinib treatment markedly differs from both imatinib- and nilotinib-treated patients.

Place, publisher, year, edition, pages
2016. Vol. 142, no 5, 1041-1050 p.
Keyword [en]
Bone marrow, Lymphocyte, CML, Tyrosine kinase inhibitor, Therapy response
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-296850DOI: 10.1007/s00432-015-2101-4ISI: 000374169900015PubMedID: 26746653OAI: oai:DiVA.org:uu-296850DiVA: diva2:940249
Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2016-06-20Bibliographically approved

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Olsson-Strömberg, Ulla
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Department of Immunology, Genetics and PathologyHaematology
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