A 37-year-old man with acute myelomonocytic leukemia (AML) M4E who exhibited the complex karyotype of 5q-, 7q-, and +22 in addition to inv(16), relapsed soon after complete remission. As previously reported, AML M4E carrying inv(16) is associated with a good prognosis, even when co-occurring with chromosomal abnormalities, which alone are considered to have poor outcome. Cytogenetic prognosis studies, such as CALGB or SWOG, have reported that certain additional chromosomal abnormalities or complex karyotypes might affect the prognosis of patients with AML M4E with inv(16). Our case suggests that, in general, AML M4E carrying inv(16) is in the favorable risk category, while cases with additional chromosomal abnormalities or complex karyotypes might be classified in the poor risk group and thus should be given additional clinical attention.

An increase in the presence of the Ph-negative, trisomy 8 clone has been reported in chronic myelogenous leukemia (CML) under imatinib therapy, but any impact of the clone on patient prognosis remains uncertain. We report here on a 42-year-old male with CML who received imatinib after failure of interferon-alpha therapy. A chromosomal analysis revealed 18/20 trisomy 8 in bone marrow at 10 months of imatinib administration. Continuing imatinib at 300 mg daily resulted in a decrease in the number of trisomy 8 clones as well as the disappearance of Ph clone. Furthermore, the patient's pancytopenia was gradually improved. Imatinib therapy could be continued even with the emergence of trisomy 8.

Cancers are formed by heterogeneous cell types from immature highly proliferative cells to lineage-committed differentiated cells. Transplantation studies have suggested the existence of "cancer stem cells", individual cells capable of producing an entire tumor. Recent advances in stem cell research have allowed for the demonstration of the existence of cancer stem cells in acute myeloid leukemia, breast cancer, and, most recently, in pediatric brain tumors. Each of these has some similarities with the normal stem cells in the corresponding organs. For example, leukemia stem cells express some, but not all, markers of hematopoietic stem cells. Regarding pediatric brain tumors, putative cancer stem cells were identified from medulloblastoma and also from glioma. These tumor-derived cells self-renew under clonal conditions, and differentiate into neurons and glia as well as into abnormal cells with mixed phenotypes. Interestingly, the tumor stem/progenitors, enriched in culture, maintained proliferation after 4 weeks from transplantation into neonatal rat brain. In this review, we discuss the difference as well as the similarity between tumor and normal stem cells, and also the possible clinical implication of cancer stem cells.

It is important to exclude germ line mutation in cases of unilateral retinoblastoma(RB) to estimate hereditary or possible secondary cancer. We investigated whether genetic diagnosis is feasible in a health check screening program.

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS expression level of cancer tissues is a potential predictor of the response to 5-FU-based chemotherapy. The TS gene has a polymorphic tandem-repeat sequence, which is associated with its protein expression. Therefore, the TS polymorphism may also be a predictor of the response to 5-FU-based chemotherapy. In this study, we analyzed the TS genotype, TS protein level, and sensitivity to 5-fluoro-5'-deoxyuridine (5'-dFUrd) in 10 human gastric cancer cell lines. TS genotype was classified into 2R-homozygote (2R/2R, n=3), 3R-homozygote (3R/3R, n=5), and 2R/3R-heterozygote (2R/3R, n=2). The cell lines with 3R/3R showed a significantly higher IC50 value compared to those with 2R/2R or 2R/3R genotype. There was no relationship between TS protein level and 5'-dFUrd sensitivity. However, a statistically significant relationship was revealed between them when the subgroup with the genotypes of 2R/2R or 2R/3R was considered (r=0.815, p<0.05). In this subgroup, the cell lines with higher TS protein showed higher IC50 value for 5'-dFUrd, indicating less sensitivity to 5'-dFUrd. An identical relationship between the TS protein level and IC50 was also observed in the subgroup with 3R/3R genotype, although it did not reach statistical significance (r=0.745, p=0.09). These results suggest that the TS gene polymorphism and TS protein level may be independent predictors for 5-FU-based chemotherapy.

Soft tissue sarcomas (STS) are rare and heterogeneous group of tumors which differ widely in their clinicopathological features, and have a wide spectrum of clinical course, ranging from indolent tumors with a good prognosis to highly aggressive tumors with a poor prognosis. The diagnostic process of STS is complex and may necessitate an array of ancillary studies, including immunohistochemistry, electron microscopy and molecular genetic methods. Although an ongoing and improved histopathological definition of individual tumor types has been established, there still remains a subset of mesenchymal tumors which are currently not readily classifiable. This review summarizes our experience and that of others in the approach to the pathological evaluation of STS, and especially emphasizes the need to use emerging molecular techniques that can provide important clues for diagnosis, prognosis, and treatment of STS.

p53 is a molecule which is activated upon a DNA stress, such as gamma irradiation, UV, hypoxia, virus infection, and DNA damage, leading protection of cells by inducing target genes. The molecules activated by p53 induce apoptosis, cell cycle arrest, and DNA repair to conserve genome. In order to kill cancer cells, many strategies targeting p53 have been reported. Preclinical studies have demonstrated that overexpression of wt-p53 by adenovirus vector is capable of inducing apoptosis in cancers. Furthermore, restoration of mt-p53 into wild type by compound has been under development. In this review, clinical application of molecular targeting therapy for p53 is discussed.

The expression of cell surface antigens and bcl-2 protein was examined with flow cytometry in 30 lymphoma samples including 28 lymph nodes and others, from January, 2001 to May, 2003. Cases studied included the following: follicular lymphoma (FL), 11; diffuse large B-cell lymphoma (DLBCL), 12; diffuse small B-cell lymphoma, 1; mantle cell lymphoma, 1; MALT lymphoma, 1; precursor-B lymphoblastic lymphoma, 1; T-lymphoblastic lymphoma, 1; blastic NK-cell lymphoma, 1; and unknown, 1. In addition, cytogenetic analysis, fluorescence in situ hybridization (FISH), and a real-time polymerase chain reaction assay were performed. Strong bcl-2 expression was observed in 91% of FL, and 17% of DLBCL. On the other hand, strong bcl-2 expression was found in all 9 cases of FL with t(14;18), all two cases of DLBCL with t(14;18), one unknown case with t(14;18), and one FL case with t(11;14). Our results support that strong bcl-2 expression as demonstrated with flow cytometry is correlated with FL (p<0.0001), and lymphomas with the t(14;18) (p<0.0001).

Mismatches of minor histocompatibility antigens (mHas) between HLA-identical stem cell donors and recipients are known as a major risk factor for graft-versus-host disease (GVHD). We determined the alleles of 5 polymorphic molecules including HA-1 and 4 adhesion molecules in 102 patients who had undergone stem cell transplantation from HLA-identical donors and investigated the association of their mismatches with the relapse rate and incidence of GVHD. We observed relapse rates of 16.1% in patients with at least one or more incompatibilities and 39.4% in patients without incompatibilities (p = 0.018). The respective relapse rates of patients with CD62L, HA-1, CD31 exon 563, CD31 exon 125 and 49b incompatibilities were 6.1%, 14.3%, 11.7%, 20% and 40%. Only patients with CD62L incompatibilities showed a lower relapse rate than patients who received a compatible graft. Since there was no difference between patients with and without incompatibilities as far as the appearance of acute GVHD (> or = 2) was concerned, we conclude that the polymorphic CD62L molecule contributes to graft-versus-leukemia rather than the development of GVHD after HLA-identical stem cell transplantation.