Nguyen T. Van

Quantitation of minimal residual disease in acute myelogenous leukemia and myelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells

Detection of karyotypic clonal abnormalities are prognostically useful in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS), but cytogenetic methods are not sensitive enough to detect low numbers of residual leukemic cells in patients who have achieved complete remission (CR). Fluorescence in situ hybridization (FISH) and fluorescence activated cell sorting (FACS) were used to investigate the frequency and presence of minimal residual disease (MRD) in AML and MDS patients (n = 28) with monosomy of chromosomes 7, 17 and 18 and trisomy of chromosomes 6, 8, 9 and 10 in CR. MRD was detected in all patients with monosomy 7 (n = 10) and followed by relapse in eight patients after 4.8 ± 3.1 months. In contrast, persistent leukemic cells occurred in 11/12 patients with trisomy 8, but only three of them relapsed after 7.7 ± 4.0 months. Cox regression analysis showed that cytogenetic class and levels of clonal cells at CR were related to time to relapse (P = 0.001). The level of MRD identified patients at high and low risk of relapse. High absolute levels of proliferating residual leukemic cells correlated with monosomy 7 and high risk of relapse.

Minimal residual disease in acute myelogenous leukaemia and myelodysplastic syndromes: a follow‐up of patients in clinical remission

The majority of patients with acute myelogenous leukaemia (AML) and myelodysplastic syndromes (MDS) relapse, especially those with unfavourable cytogenetics.

Structural analysis of the C-CAM1 molecule for its tumor suppression function in human prostate cancer.

Recently, we demonstrated that expression of C‐CAM1, an immunoglobulin (Ig)‐like cell adhesion molecule (CAM), was diminished in both prostate intraepithelial neoplasia and cancer lesions, indicating that loss of C‐CAM1 expression may be involved in the early events of prostate carcinogenesis. Also, increased C‐CAM1 expression can effectively inhibit the growth of prostate cancer. Structurally, C‐CAM1 represents a unique CAM with a potential signal transducing capability. In this study, we further analyzed the functional domain of C‐CAM1 for controlling its tumor suppression function.

The phosphorylation of retinoblastoma gene product in human myeloid leukenia cells during the cell cycle

Counterflow centrifugal elutriation and immunoblotting techniques were used to study the expression of the retinoblastoma (RB) gene during the cell cycle of BV173 chronic myeloid leukemia (CML) cells. Our data showed that Rb protein started to be phosphorylated at early G1 phase, became hyperphosphorylated when cells progressed to late G1 and S phases during cell cycle, and remained hyperphosphorylated throughout S and G2/M phases. Our data suggest that Rb phosphorylation starts at a more distal point to the G1/S phase boundary in human myeloid leukemia BV173 cells rather than at a point more proximal to the G1/S boundary, as seen in HeLa cells.

Elevated expression of hepatic proliferative markers during early hepatocarcinogenesis in hepatitis-B virus transgenic mice lacking mdr1a-encoded P-glycoprotein.

Recent studies have shown that expression levels of the multidrug resistance gene MDR1, which encodes the drug transporter P‐glycoprotein, correlate with prognostic outcomes of certain tumor types. These findings suggest that expression of MDR1 may affect tumor behaviors. To address this issue further, we investigated the expression of mdr1a, a human MDR1 homolog, on the development of hepatocellular carcinoma in a transgenic mouse model carrying the liver‐targeted expression of human hepatitis‐B virus (HBV) surface antigen. The pathogenetic program was compared in HBV mice carrying either mdr1a(+/+) or mdr1a(−/−). We found that the expressions of proliferative activity markers, Ki67 nuclear antigen, and proliferating cell nuclear antigen were elevated in mdr1a(−/−) mice younger than 10 wk in comparison with those in the same age group of wild‐type animals. Replication in the hepatic population as determined by bromodeoxyuridine incorporation tended to support observation that mdr1a(−/−) mice exhibited elevated labeling indices in this age group. Moreover, histologic staining and flow‐cytometric analysis showed that the mdr1a(−/−) animals exhibited a higher cell population with polyploidy than did the mdr1a(+/+) counterparts of the same age. However, no significant differences in the expression of the liver‐injury markers serum alanine transaminase and aspartate transaminase were observed. Although our results showed that absence of mdr1a expression is correlated with modest enhanced proliferative characteristics in the livers at stage before the development of hepatocellular carcinoma, the overall life spans between these two strains of mice were not significantly different. The implication of these findings to the role of P‐glycoprotein in tumor development and cancer chemotherapy is discussed. Mol. Carcinog. 29:103–111, 2000.