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High levels of expression of Wilms' tumor gene 1 ( WT1), survivin, or telomerase reverse transcriptase ( TERT) genes are introduced as leukemia-associated targets predicting clinical outcome. We prospectively investigated the leukemia-associated gene transcripts by real-time quantitative polymerase chain reaction from 151 adult patients with AML associated with the patients' clinical characteristics. The maximum levels of each gene in bone marrow were 64.4-, 8.1-, and 3.9-fold higher than those in the normal control, respectively. In contrast to the WT1 and TERT levels, survivin showed comparatively higher expression in the unfavorable cytogenetic group of patients. We found a significant difference in s urvivin levels between the CR and non- CR groups ( P = 0.0237). TERT expression levels were higher in patients who had a greater number of peripheral blood leukemic blasts at diagnosis ( P = 0.0191). Non- MRC subtypes and patients without specific mutations were the most powerful predictive factors for a better CR rate, by multivariate analyses. The lower levels of both WT1 and survivin co-expression ( P = 0.0129) and both survivin + TERT co-expression ( P = 0.0115) were significant factors for better OS. Besides lower initial levels of serum ferritin ( P = 0.0401), lower levels of WT1 ( P = 0.0438) and survivin ( P = 0.0401), lower levels of both WT1 and survivin co-expression ( P = 0.0031), and the three-gene combination of lower WT1 + survivin + TERT ( P = 0.0454) were powerful predictive factors for better EFS. As our findings were based on a single disease entity, that is, adult AML, they suggest that the expression of these genes may be critical for the immunobiology of AML to influence the clinical outcome in various ways. [ABSTRACT FROM AUTHOR]

Specific immunotherapies for CML patients targeting T cell antigens might eliminate residual CML cells after chemotherapy, in combination with imatinib or other tyrosine kinase inhibitors, and might enhance a specific graft versus leukemia effect after allogeneic stem cell transplantation without aggravating the graft versus host disease. For an effective specific immunotherapy in CML, the use of leukemia-associated antigens (LAAs) with an optimal expression pattern is required. In this work, we review known LAAs which are able to induce specific CD8 positive T cell responses and which are appropriate target structures for immunological targeting of CML cells. Moreover, an overview on LAA-targeted immunotherapeutic approaches for CML patients are given. [ABSTRACT FROM AUTHOR]

Objectives: Aberrant expression of cyclin B1, a cell cycle regulator, is related to prognosis in various human malignancies. Additionally, cytoplasmic expression of cyclin B1 in epithelial malignancies is associated with a specific T-cell response and presumably also a humoral immune response. We therefore investigated (i) whether a similar expression pattern could be detected in native human acute myelogenous leukemia (AML) cells and (ii) whether cyclin B1 specific antibodies could be detected in AML. Methods: AML cell expression of cyclin B1 was analyzed by flow cytometry and confocal microscopy. Humoral immune response in AML patient sera against cyclin B1 was analyzed by ELISA. Results: AML cell expression of cyclin B1 was detected for all 42 patients; but the percentage of cyclin B1 positive cells showed a wide variation between patients. Confocal microscopy demonstrated that 32/42 (76%) patient samples showed abnormal cytoplasmic expression. Furthermore, the cytoplasmic expression was maintained after 14 d of in vitro culture and differentiation of the AML cells towards a dendritic cell phenotype. Cyclin B1 specific serum antibodies could be detected for seven of 65 patients with untreated AML. Conclusions: Our studies demonstrate that primary human AML cells show aberrant cytoplasmic expression of cyclin B1 for a majority of patients and a specific humoral immune response was also detected for a subset of patients with untreated leukemia. [ABSTRACT FROM AUTHOR]