PURPOSE Multidrug resistance mediated by several drug resistant genes impedes the successful outcome of anti-cancer chemotherapy. In this study, we investigated the expressions of drug resistant genes encoding multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), topoisomerase I (Topo I), topoisomerase II g (Topo II a) in narmal volunteers (n=12) in and patients with myeloid leukemia (n=34). Material and Method: We compared the levels of their transcripts in bone matrow mononuclear cells by semiquantitative RT-PCR. The amount of specific transcripts was represented as the optical density ratio of PCR product of target gene to that of B2- microglobulin (MG). Twenty patients of acute myelogenous leukemia (eight in remission state, twelve in refractory) and fourteen patients of chronic myelogenous leukemia (nine in chronic phase and five in blastic crisis) were examined. Twelve normal healthy persons were compared with leukemic patients. RESULTS The expression levels of all resistant genes in normal volunteers were relatively high as those of AML patients. Regardless of the disease status including remission status of AML (complete remission versus refractory) and the phase of CML (chronic phase versus blastic phase), the expression levels of all resistant genes in patients with CML were significantly lower than in the patients with AML (p < 0.05). Of interest, the patients with refractary AML did not show any statistical difference in comparison with normal controls and even the patients with AML in complete remission. Among the four drug resistant genes, the optical density ratio of MDRl was significantly lower than that of any other genes (p<0.05). Using HL-60 cell line, we compared the changes of various resistant gene expressions before and after differentiation induced by dimethylsulfoxide. The expressions of resistant genes declined in paralle1 with granulocytic differentiation, suggesting that the induction of cell differentiation might make leukemic cells susceptible to chemotherapeutic agents. CONCLUSION It is impossibble to explain the mechanism of drug resistance by comparing the level of drug resistant gene expression between nonnal subjects and patients with myeloid leukemias. Therefore, we suppose that longitudinal study of drug resistant gene expression is necessary to demonstrate the development of drug resistant during chemotherapy.
The CD34 antigen is a 115 kDa glycoprotein that marks 1%-4% of human bone marrow cells, including virtually all committed progenitor cells and long-term reconstituting stem cells. The selection of CD34+ cells may be useful in several areas of clinical stem cell transplantation, including purging of tumor cells, T cell depletion, stem cell expansion and gene therapy. Using immunomagnetic beads method (Isolex-50TM), we report hereby the first two Korean experiences of CD34+ selected peripheral blood stem cell (PBSC) transplantations. As a mean of tumor cell purging, CD34+ cells were positively selected from mobilized PBPCs and infused to a 5-year-old girl with a relapsed stage IV neuroblastoma with resultant early short-term trilineage hematopoietic recovery. In the second patient with chronic myelogenous leukemia who showed poor graft function after having underwent an initial partially-matched bone marrow transplant, CD34+ selected allogeneic PBSC transplantation was attempted to reduce the likelihood of inducing graft-versus-host disease. Augmentation of marrow function was noted with infused PBSCs which were depleted of T cells to the degree of log3.65. As CD34+ selected PBSCs are capable of restoring hematopoietic recovery after high dose therapy, further development of selection technique to ensure high purging efficiency without significant loss of stem cells and further identification of best mobilizing and conditioning regimens are required in this new field of clinical transplantation.
The incidence of multiple primary cancer is increasing recently due to various reasons. A case of gastric cancer was developed during the course of treatment of CML and the interval between CML and subsequently found gastric adenocarcinoma was l6 months. We report a case of gastric adenocarcinoma with CML with review of literature.