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)

Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.
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PMID:The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. 158 43

Although CD4(+) helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4(+) T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4(+) T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4(+) T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4(+) T lymphocyte clones produced interferon-gamma (IFN-gamma) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-gamma production by CD4(+)T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4(+) T lymphocytes.
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PMID:Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes. 1245 45