Hypoplastic acute leukemia associated with inv(16)(p13q22).
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Biomedical subjects
Publications and source records attributed to N Sadamori.
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Nineteen patients with acute nonlymphocytic leukemia (ANLL) de novo who had no detectable chromosomal abnormalities received intensive remission induction chemotherapy. After the first chemotherapy cycle, ten of 14 (71%) patients aged 60 years or less entered complete remission (CR) whereas none of five patients aged more than 65 years attained CR. On the other hand, leukemia showed a drug resistance in three (21%) of the former patients and in four (80%) of the latter patients. One patient in each group died during induction. Generally, older ANLL patients have an inferior CR rate after chemotherapy and a poor prognosis. This has been explained by the facts that the risk of induction death increases and that specific chromosomal abnormalities associated with poor prognosis are considerably more frequent in older patients. Our data may indicate, however, that in ANLL with normal karyotype older patients show a low initial response rate because of drug resistance.
The close association between adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) has been established. Nevertheless, the mechanism of progression of ATL by HTLV-I infection is still uncertain, because the virus contains no typical oncogene and no significant expression of the viral RNA has been generally found. I propose a model of leukemogenic process in ATL based on our cytogenetic data and molecular results in the literature. It seems that the rearrangement of some proto-oncogene and alpha-chain gene of the T-cell antigen receptor (TCR-alpha) is necessary for the development to overt ATL. A deficiency in the rearrangement of proto-oncogene to TCR-alpha may result in only a minor proliferation of abnormal lymphocytes and remain in the preleukemic state of ATL or in the HTLV-I carrier state.
The relationship between chromosome breakpoints associated with T-cell antigen receptor (TCR) genes and TCR-alpha/beta/tau/delta rearrangements of peripheral leukaemic cells in 8 Japanese patients with the acute type of adult T-cell leukaemia (ATL) was examined. Break of the 14q11 region with the assigned locus of TCR-alpha/delta was revealed in 6 patients, interstitial deletion of the 7q32-36 region with assigned locus of TCR-beta in 1 patient, and break of the 7p15 region with assigned locus of TCR-tau in 2 patients. Molecular analysis revealed TCR-alpha rearrangement in 7 patients, TCR-beta rearrangement in all patients, and TCR-tau rearrangement in 5 patients. TCR-delta was deleted in all patients. These findings indicate a close relationship between 14q11 anomaly and TCR-alpha rearrangement, which may play an important role in the leukaemogenesis of ATL.
Of the 66,276 Nagasaki atomic bomb survivors registered at the Scientific Data Center for the Atomic Bomb Disaster at the Nagasaki University School of Medicine, 140 were identified as having skin cancer from the records of 31 hospitals in Nagasaki City. From the cases of these survivors, a statistical analysis was made of the incidence of skin cancers by age, gender, histology and latency period in Nagasaki atomic bomb survivors. The results showed a high correlation between the incidence of skin cancer and distance from the blast hypocenter, and that the incidence of skin cancer in the Nagasaki survivors appears now to be increasing with exposure distance.
This report describes three of primary bilateral adrenal lymphoma. Case 1 was an 87-year-old female. She was admitted to our hospital because of anemia. Masses in the bilateral adrenal glands were noted on abdominal computed tomography (CT). After combination chemotherapy, bilateral adrenal masses transiently showed a remarkable reduction, but they soon enlarged and she died. The pathological diagnosis at autopsy was non-Hodgkin lymphoma (diffuse medium sized cell type). Case 2 was a 77-year-old male. He visited our hospital complaining of general malaise. Masses in the bilateral adrenal glands were noted on abdominal CT and he was admitted. The left adrenal was biopsied under echo guidance. The pathological diagnosis was non-Hodgkin lymphoma (diffuse medium sized cell type). The bilateral adrenal masses transiently responded to combination chemotherapy, but soon enlarged again and he died. Case 3 was a 75-year-old male. He visited our hospital complaining of general malaise. Masses in the bilateral adrenal glands was noted on abdominal CT and he was admitted. The left adrenal was biopsied under echo guidance. The pathological diagnosis was non-Hodgkin lymphoma (diffuse medium sized cell type). Combination chemotherapy was followed by a complete remission and discharge of the patient.
We performed cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis in two cases of juvenile chronic myeloid leukemia (JCML) which is special type of chronic myeloid leukemia (CML). Case 1 (8-month-old male) and case 2 (3-month-old female) showed clinical and hematologic manifestations similar to CML. Each of case 1 and 2 had normal karyotype and no bcr rearrangement. These findings suggest that JCML is a different heterogeneous disorder from that of adult CML.
A 30-year-old man was referred because of slight leukocytosis. The hematological findings, including those of the bone marrow, showed no evidence of leukemia. The level of neutrophil alkaline phosphatase (NAP) in the peripheral blood was normal, as were the chromosomes from bone marrow cells. Fifteen months later, the disease was diagnosed as M2 (according to the French-American-British classification) showing a t(8;21)(q22;q22) and a low NAP level as two markers of M2 cells. This is probably the first case of acute leukemia in which the cytogenetic analysis was performed before and after the appearance of a specific chromosome abnormality.
Recently, the chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL), and this anomaly has also been confirmed in the preleukemic state of adult T-cell leukemia (pre-ATL) patients. Because the cytogenetic abnormality at the stage of human T-cell leukemia virus type I (HTLV-I) carrier remains uncertain, we performed cytogenetic studies of lymphocytes stimulated with phytohemagglutinin in three HTLV-I carriers and three non-HTLV-I carriers in an ATL family. As a result, in three HTLV-I carriers, four of 311 cells examined (1.3%) had chromosome 14q11 anomaly. However, in three non-HTLV-I carriers, none of 260 cells examined had chromosome 14q11 anomaly. These results suggest that chromosome 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL.
We describe 5 cases of adult T-cell leukemia (ATL) carrying translocations at chromosome 14q11, where the genes for alpha- and delta-chains of the T-cell receptor (TCR alpha/delta) reside (Croce et al., 1985; Isobe et al., 1988). Since the TCR alpha/delta locus is the region where several types of chromosome translocations occur in T-cell tumors, rearrangements of the TCR alpha/delta locus in those ATL cases were studied as a first step to characterize these translocations at the molecular level. For this purpose we have generated an extensive series of probes to define the specificity and the diversity of rearrangement occurring at the widely spanned J alpha-C alpha locus and the complex D delta-J delta-C delta-V delta 2 locus. Using a set of probes, we have found the deletion of the TCR delta locus in all ATL cases, and at least 2 rearrangements in the J delta locus in each case of ATL. It is possible that translocations in the TCR alpha locus may be involved in ATL.
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Chromosome findings in cultured skin fibroblasts from a patient treated with an anti-cancer drug, pepleomycin sulfate, for his penis cancer are reported. In two batches of specimens (days 16 and 34, respectively), out of 120 cells examined, a total of 26 abnormal cells (21.7%) were found with no common chromosome abnormalities; there were no clones. This cytogenetic pattern of abnormalities without clones in cultured skin fibroblasts differs from that seen in congenital disease or radiation-exposed skin fibroblasts. It is suggested that the anti-cancer agent is the most likely etiological factor for these uncloned chromosome abnormalities in cultured skin fibroblasts.
Two patients with acute nonlymphocytic leukemia (ANLL) and t(16;21)(p11;q22) were studied. The patients exhibited such clinical and hematological pictures, characterized by M2 and M4 with eosinophilia (FAB classification), as relatively matured leukemic cells, low neutrophil alkaline phosphatase activity, abnormal eosinophils and a high count of monocytic cells in the bone marrow. The prognosis was poor in both patients. From these data, the chromosomal abnormality of t(16;21)(p11;q22) seems to be specifically associated with a unique subtype of ANLL.
Among a total of 65,268 Nagasaki atomic bomb survivors recorded in the Scientific Data Center of Atomic Bomb Disaster, Nagasaki University School of Medicine, 140 cases with skin cancer were collected from 31 hospitals in Nagasaki City from 1961 through 1987. Subsequently, these cases of skin cancer in Nagasaki atomic bomb survivors were statistically analyzed in relation to the estimated distance from the hypocenter by age, sex, histology and latent period. The results were as follows: 1. A high correlation was observed between the incidence of skin cancer and the distance from the hypocenter. 2. The incidence of skin cancer in Nagasaki atomic bomb survivors now appears to be increasing in relation to exposure distance. 3. Among 140 cases, basal cell epithelioma was observed in 67 cases (47.9%) and squamous cell carcinoma in 43 cases (30.7%).
To clarify the clinical significance of serum deoxythymidine kinase in various hematological disorders, basic examination was performed of a newly developed radioenzyme assay kit for TK (Prolifigen TK kit "Daiichi") using 125I-iodo-deoxyuridine as a substrate. The assessment of the standard curve, and the results of recovery test, dilution test, and precision and reproducibility were satisfactory. Among several anticoagulant agents tested, heparin was the best one showing no influence on the measurement of TK level. Based on these results, serum TK level was measured in 140 healthy adults as a control group. There was no difference by age and sex. The serum TK level of normal control was 3.1 +/- 1.2 U/l, with an upper limit of 5.5 U/l.
Using Prolifigen TK kit "Daiichi", the serum TK level were determined in patients with adult T-cell leukemia (ATL) and its related disorders. The mean level of serum TK at diagnosis was 279.9 U/l in acute type ATL, 27.8 U/l in chronic type ATL, 59.0 U/l in lymphoma type ATL, 3.1 U/l in pre-ATL and 2.4 U/l in HTLV-I carriers. In these patients, six other kinds of tumor markers such as lactic dehydrogenase, beta 2-microglobulin, immunosuppressive acidic protein, ferritin, tissue polypeptide antigen and carcinoembryonic antigen were also examined. Among the seven tumor markers, TK level showed the most significant difference among clinical subtypes of ATL. This indicates that the TK level is one of the promising parameters indicative of aggressiveness of ATL cells.
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The acute lymphoblastic cell lines designated BAL-KHc and BAL-KHs were established from the peripheral blood of a Japanese female patient with a B-cell acute lymphoblastic leukemia. The BAL-KHc and BAL-KHs exhibited B-cell characteristics with positive cell markers for CD19, CD20, CD21 and HLA-DR antigens. Immunoglobulin with gamma and kappa chains was demonstrated on the cultured and fresh leukemia cells respectively. The cells lacked the Epstein-Barr virus genome and expressed abnormal chromosome constitutions including a t(8;14)(q24;q32). These results suggested that the cell lines present B-cell characteristics. The BAL-KHc cells showed different cell growth characteristics and cell surface marker profile compared to those of the BAL-KHs. These variations suggest that the BAL-KHc cells were probably frozen at a different stage of B-cell maturation from those of BAL-KHs, although both cell lines originated from the cells in the same peripheral blood sample of the patient.