Nejvíce citovaný článek - PubMed ID 17545631
Acute myeloid leukemia with mutated nucleophosmin (NPMc+ AML) forms a distinct AML subgroup with better prognosis which can potentially be associated with immune response against the mutated nucleophosmin (NPM). As the T-cell-mediated immunity involves antigen presentation on HLA class I molecules, we hypothesized that individuals with suitable HLA type could be less prone to develop NPMc+ AML. We compared HLA class I distribution in NPMc+ AML patient cohort (398 patients from 5 centers) with the HLA allele frequencies of the healthy population and found HLA-A*02, B*07, B*40 and C*07 underrepresented in the NPMc+ AML group. Presence of B*07 or C*07:01 antigen was associated with better survival in patients without concomitant FLT3 internal tandem duplication. Candidate NPM-derived immunopeptides were found for B*40 and B*07 using prediction software tools. Our findings suggest that a T-cell-mediated immune response could actually explain better prognosis of NPMc+ patients and provide a rationale for attempts to explore the importance of immunosuppressive mechanisms in this AML subgroup.
- MeSH
- akutní myeloidní leukemie * genetika imunologie mortalita MeSH
- buněčná imunita * MeSH
- dospělí MeSH
- jaderné proteiny * genetika imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- MHC antigeny I. třídy * genetika imunologie MeSH
- míra přežití MeSH
- nádorové proteiny * genetika imunologie MeSH
- nukleofosmin MeSH
- prevalence MeSH
- přežití bez známek nemoci MeSH
- senioři MeSH
- T-lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- jaderné proteiny * MeSH
- MHC antigeny I. třídy * MeSH
- nádorové proteiny * MeSH
- NPM1 protein, human MeSH Prohlížeč
- nukleofosmin MeSH
Treatment with imatinib mesylate and other tyrosine kinase inhibitors (TKI) revolutionized the therapy of chronic myeloid leukemia (CML). However, it alone does not cure this disease. Moreover, some patients develop resistance or adverse effects to this therapy. As successful treatment of a portion of CML patients by hematopoietic stem cell transplantation (HSCT) suggests the importance of immune mechanisms in the elimination of leukemic cells, including leukemia stem cells, TKI administration or HSCT might be combined with vaccination to cure CML patients. However, antigens implicated in the immune responses have not yet been sufficiently identified. Therefore, in this report, we compiled and characterized a list of 165 antigens associated with CML (CML-Ag165) and analyzed the expression of the corresponding genes in CML phases, subpopulations of leukemic cells, and CML-derived cell lines using available datasets from microarray transcriptional-profiling studies. From the CML-Ag165 list, we selected antigens most suitable for vaccine development and evaluated their appropriate characteristics.
- MeSH
- antigeny nádorové imunologie MeSH
- chronická myeloidní leukemie imunologie MeSH
- lidé MeSH
- protinádorové vakcíny * MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antigeny nádorové MeSH
- protinádorové vakcíny * MeSH