BACKGROUND: Apoptosis is a physiologic phenomenon involved in development, elimination of damaged cells, and maintenance of cell homeostasis. Deregulation of apoptosis may cause diseases, such as cancers, immune diseases, and neurodegenerative disorders. The mouse myeloma cell P3-X63-Ag8.653 (v653) is an HGPRT deficient (HGPRT) mutant strain. High dependency on de novo transcription and translation of aminopterin induced apoptosis of this cell seems to be an ideal experimental system for searching apoptosis-induced genes. METHODS & RESULTS: For searching apoptosis-related genes we carried out GE-array (dot blot), Affymetrix GeneChip analysis, Northern analysis and differential display-PCR techniques. The chip data were analyzed with three different programs. 66 genes were selected through Affymetrix GeneChip analyses. All genes selected were classified into 8 groups according to their known functions. They were Genes of 1) Cell growth/maintenance/death/ enzyme, 2) Cell cycle, 3) Chaperone, 4) Cancer/disease-related genes, 5) Mitochondria, 6) Membrane protein/signal transduction, 7) Nuclear protein/nucleic acid binding/ transcription binding and 8) Translation factor. Among these groups number of genes were the largest in the genes of cell growth/maintenance/death/enzyme. Expression signals of most of all groups were peaked at 3 hour of apoptosis except genes of Nuclear protein/nucleic acid binding/ transcription factor which showed maximum signal at 1 hour. CONCLUSION: This study showed induction of wide range of proapoptotic factors which accelerate cell death at various stage of cell death. In addition apoptosis studied in this research can be classified as a type 2 which involves cytochrome c and caspase 9 especially in early stages of death. But It also has progressed to type 1 in late stage of the death process.
Aminopterin ; Animals ; Apoptosis ; Caspase 9 ; Cell Cycle ; Cell Death ; Cytochromes c ; Homeostasis ; Hypoxanthine Phosphoribosyltransferase ; Immune System Diseases ; Membranes ; Mice ; Mitochondria ; Neurodegenerative Diseases ; Transcription Factors

Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination che-motherapy, but her leukemic cells were resistant to the therapy.
Adult ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; B-Lymphocytes/cytology ; Bone Marrow Cells/pathology ; Carmustine/*adverse effects ; Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; Combined Modality Therapy/adverse effects ; Cyclophosphamide/*adverse effects ; Cytarabine/*adverse effects ; Etoposide/*adverse effects ; Female ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Leukemia, Myeloid, Acute/*etiology/genetics ; Lymphoma, Non-Hodgkin/*therapy ; Myelodysplastic Syndromes/*etiology/genetics ; Neoplasms, Second Primary/*etiology ; Pelvis ; Pregnancy ; Pregnancy Complications, Neoplastic/*therapy ; Transplantation, Autologous