ABSTRACT
BACKGROUND: Aplastic anemia(AA), myelodysplastic syndrome(MDS) and paroxysmal nocturnal hemoglobinuria(PNH) are hematopoietic stem cell disorders. To investigate the pathogenetic links, we performed CD59 analysis and screened PIG-A gene mutation in the patients with AA, MDS, and PNH developed from AA or MDS. METHODS: We analyzed the proportion of the patients with CD59-deficient cells by flow cytometry for CD59 in 42 patients with AA or MDS and eight patients with PNH developed from AA or MDS. The mutations of PIG-A gene were screened with dideoxy fingerprinting(ddF). RESULTS: In normal controls, the proportion of the RBCs normally expressing CD59 was 97.2+/-1.9% and that of the granulocytes was 98.4%+/-1.5%. In patients with AA or MDS, 9.5%(4/42) had CD59 deficiency on RBCs and 10.3%(3/29) on granulocytes. In patients whose CD59 on both RBCs and granulocytes were analyzed, 17.2%(5/29) showed reduced CD59 in at least one cell lineage. Screening test using ddF revealed abnormal band shifts in three patients with PNH developed from AA or MDS. CONCLUSION: We found the presence of PNH clones in the patients with AA or MDS. And it was indirectly confirmed by ddF that PNH arisen from AA or MDS is also associated with the mutations of PIG-A gene as classical PNH. CD59 analysis in AA or MDS will be helpful for the early diagnosis of PNH.
Subject(s)
Humans , Anemia, Aplastic , Cell Lineage , Clone Cells , Early Diagnosis , Flow Cytometry , Granulocytes , Hematopoietic Stem Cells , Hemoglobinuria, Paroxysmal , Mass Screening , Myelodysplastic SyndromesABSTRACT
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by deficient biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in hemopoietic stem cells. Mutation of phosphatidyl inositol glycan class A (PIG-A) gene, an X-linked gene that participates in the first step of GPI anchor biosynthesis, is responsible for PNH. Characteristics of somatic mutation of PIG-A gene in the Korean patients with PNH and their relationships to clinical characteristics were analyzed. METHODS: Twenty five patients with PNH and a donor of bone marrow transplantation were selected. Ham tests, sucrose hemolysis tests and CD59 expressions of erythrocytes and granulocytes were performed to confirm diagnosis. Dideoxy fingerprinting (ddF) was used to screen mutations, and direct sequencing of DNA was performed to characterize the mutations. RESULTS: The mutations of PIG-A gene were found in twelve cases and ten of them were novel mutations. There were five deletions, six substitutions and a insertion. Therewere six premature terminations, three abnormal splicings, a missense and two nonsense mutations. There were six point mutations and six frameshift mutations. Five cases of hypoplastic PNH showed mutations only in exons, but three in seven cases of hemolytic PNH showed mutations in introns. Two cases with symptoms of venous thrombosis showed mutations in exon 3. CONCLUSION: There were ten novel mutations among twelve mutations in the Korean patients with PNH and characteristics of the mutations were variable without any remarkable hot spot in sites and types. The characteristics of mutation were not correlated with the results of clinical courses of the patients with PNH.
Subject(s)
Humans , Bone Marrow Transplantation , Codon, Nonsense , Dermatoglyphics , Diagnosis , DNA , Erythrocytes , Exons , Frameshift Mutation , Genes, X-Linked , Glycosylphosphatidylinositols , Granulocytes , Hemoglobinuria, Paroxysmal , Hemolysis , Introns , Phosphatidylinositols , Point Mutation , Stem Cells , Sucrose , Tissue Donors , Venous ThrombosisABSTRACT
Eight patients with malignant tumors, testified by pathological examination. were treated by " Two-Route Chemotherapy" using a high dose of HD-Cisp latine in arterial infusion (AI). Among them 5 cases were primary or metastatic liver carcinoma, 3 cases were Ⅲ-Ⅳ stage breast carcinoma.One or two courses were given in each patient. The dosage of DDP in the first course was 80 - 100mg/m~2. the second was 120-150mg/m~2 with STS Ⅳ as a protective agent. The total lasted 14 courses.When DDF was given alone in AI, the serum creatine level increased temporarily, but there was no significant increase when both DDP and sodi um thiosulfate were given.Results: Among 5 cases of liver carcinomas I was complete response 3 were partial response and 1 was stable. Among 3 cases of Ⅲ-Ⅳ stage of breast carcinomas, all were partial response, giving a response rate of 8 (?) (7/8).