Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer testis (CT) antigens provide attractive targets for cancer-specific immunotherapy. Although CT genes are expressed in some normal tissues, such as the testis and in some cases placenta, these immunologically protected sites lack MHC I expression and as such, do not present 'self' antigens to T cells. To date, CT genes have been shown to be expressed in a range of solid tumours, but rarely in haematological malignancies. We have extended previous studies to investigate the expression of a comprehensive range of CT genes (MAGE-A1, -A3, -A6, -A12, BAGE, GAGE, HAGE,LAGE-1, NY-ESO-1 and RAGE) for their expression in a cohort of acute and chronic myeloid leukaemia patient samples. CT expression was not detected in 20 normal bone marrow or peripheral blood stem cell samples. In acute myeloid leukaemia (AML) nine of the 26 (35%) samples analysed expressed one or more of the CT genes with six of the samples (23%) expressing HAGE. In chronic myeloid leukaemia (CML) 24 of 42 (57%) presentation chronic myeloid leukaemia (CML) patient samples expressed one or more CT antigen with 23 expressing HAGE. We have shown that HAGE is frequently expressed in CML, and to a lesser extent in AML patient samples. This is the first demonstration of HAGE gene expression in myeloid leukaemia patients and the frequent expression of HAGE at disease presentation opens up the possibility of early immunotherapeutic treatments.
 ...
PMID:Frequent expression of HAGE in presentation chronic myeloid leukaemias. 1239 67

Specific immunotherapies for patients with chronic myeloid leukemia (CML) might eliminate residual CML cells after therapy with imatinib or chemotherapy and might enhance a specific graft-versus-leukemia effect after allogeneic stem cell transplantation. Here, we investigated the mRNA expression and T-cell recognition of tumor-associated antigens or leukemia-associated antigens (LAAs) in 34 patients with CML. Several LAAs are expressed in CML and therefore are candidate structures for specific immunotherapies: bcr-abl (100%), G250 (24%), hTERT (53%), MPP11 (91%), NEWREN60 (94%), PRAME (62%), Proteinase3 (71%), RHAMM/CD168 (83%), and WT1 (53%), but not BAGE, MAGE-A1, SSX2, or NY-ESO-1. The frequency of mRNA expression of RHAMM/CD168, Proteinase3, and PRAME was higher in acceleration phase and blast crisis. In flow cytometry, CD34+ progenitor cells typed positive for HLA molecules but were deficient for CD40, CD80, CD83, and CD86. However, RHAMM/CD168 R3-peptide (ILSLELMKL)-specific T-cell responses in CML patients were demonstrated by ELISPOT analysis and specific lysis of RHAMM/CD168 R3-pulsed T2 cells and CD34+ CML cells in chromium-51 release assays. RHAMM-R3-specific T cells could be phenotyped as CD8+R3*tetramer+CD45RA+CCR7-CD27- early effector T cells by tetramer staining. Therefore, vaccination strategies inducing such RHAMM-R3-directed effector T cells might be a promising approach to enhance specific immune responses against CML cells.
 ...
PMID:Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules. 1715 68