Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-α, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.

• Klíčová slova
• 3-dioxygenase, CML, chronic myeloid leukemia, IDO, indoleamine 2, 3-dioxygenase, INFα, interferon- α, INFγ, interferon-γ, KTI, kynurenine/tryptophan index, KYN, kynurenine, NK, natural killer, PBMC, peripheral blood mononuclear cells, Ph+, Philadelphia chromosome positive, T regs, regulatory T cells, TDO, tryptophan 2, 3-dioxygenase, TKI, tyrosine-kinase inhibitors, TRY, tryptophan, UA, uric acid., chronic myeloid leukemia, indoleamine 2, kynurenine, tryptophan metabolism, uric acid,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells that has been recognized as a disease responsive to immunotherapy. Despite the huge success of the tyrosine kinase inhibitors (TKIs), CML remains for the most part incurable, probably due to treatment resistance of leukemic stem cells, which are responsible for rapid disease relapse after discontinuation of therapy. Only allogeneic stem cell transplantation enables disease eradication. In addition to the Bcr-Abl1 oncoprotein, TKIs also inhibit off-target kinases (e.g. c-kit, Src, Tec), some of them having physiological functions in immune responses. In vitro studies have implied immunomodulatory effects of TKIs and interferon-alpha (IFN-α), but comprehensive information from in vivo analyses is missing. This review summarizes the recent advances in the field of immunology of CML, including basic information about leukemia-associated antigens and peptide vaccines, that could lead to the incorporation of TKIs and IFN-α in future therapeutic, potentially curative, interventions for CML.

• MeSH
• antigeny nádorové chemie   imunologie   MeSH
• chronická myeloidní leukemie imunologie   terapie   MeSH
• imunitní systém účinky léků   imunologie   MeSH
• imunologické faktory terapeutické užití   MeSH
• imunoterapie MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• interferon alfa metabolismus   terapeutické užití   MeSH
• lidé MeSH
• protinádorové vakcíny imunologie   terapeutické užití   MeSH
• signální transdukce účinky léků   MeSH
• subjednotkové vakcíny imunologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH
• imunologické faktory MeSH
• inhibitory proteinkinas MeSH
• interferon alfa MeSH
• protinádorové vakcíny MeSH
• subjednotkové vakcíny MeSH

In the previous paper of ours we compared, prior to start any treatment, a number of immunological parameters in 24 chronic myeloid leukemia patients with the same number of healthy subjects matched by age and sex. We found significant differences in the levels of immunoglobulins, the C4 component of complement, the C-reactive protein, interleukin 6, the composition of lymphocyte population and the production of some cytokines by stimulated CD3+ cells. Eleven of these patients were followed longitudinally. After treatment with hydroxyurea, interferon alpha, imatinib mesylate and dasatinib, or various combinations thereof, hematological remission was achieved in all patients and complete cytogenetic remission in nine of them. There was a nearly general tendency towards normalization of the abnormalities observed in the patients at their enrollment.

• MeSH
• benzamidy MeSH
• C-reaktivní protein analýza   MeSH
• chronická myeloidní leukemie imunologie   terapie   MeSH
• dasatinib MeSH
• dospělí MeSH
• hydroxymočovina terapeutické užití   MeSH
• imatinib mesylát MeSH
• imunoglobuliny krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• interferon alfa terapeutické užití   MeSH
• interleukin-6 krev   MeSH
• komplement analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• piperaziny terapeutické užití   MeSH
• přirozená imunita * MeSH
• protinádorové látky terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• T-lymfocyty metabolismus   MeSH
• thiazoly terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzamidy MeSH
• C-reaktivní protein MeSH
• dasatinib MeSH
• hydroxymočovina MeSH
• imatinib mesylát MeSH
• imunoglobuliny MeSH
• imunologické faktory MeSH
• inhibitory proteinkinas MeSH
• interferon alfa MeSH
• interleukin-6 MeSH
• komplement MeSH
• piperaziny MeSH
• protinádorové látky MeSH
• pyrimidiny MeSH
• thiazoly MeSH