Hypoplastic acute leukemia associated with inv(16)(p13q22).
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Acute Disease↗
Biomedical subjects
M Ichimaru
Publications and source records attributed to M Ichimaru.
Acute nonlymphocytic leukemia with normal karyotype. Is its in vivo drug susceptibility age-dependent?
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.
Aged↗
Relationship between chromosomal breakpoint and molecular rearrangement of T-cell antigen receptors in adult T-cell leukaemia.
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.
Aged↗
Atomic bomb and leukemia.
Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5-0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of AML subtypes by FAB classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors.
Humans↗
Atomic bomb and leukemia.
Characteristic features of leukemia among atomic bomb survivors were studied. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic for atomic bomb radiation induced leukemia. In the distribution of AML subtypes of FAB classification, there was no M3 cases in 1Gy or more group, although several atypical AML cases of survivors were observed. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral blood of proximal survivors.
Humans↗
Multiple myeloma among atomic bomb survivors.
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Humans↗
[No rearrangement of the breakpoint cluster region in two juvenile chronic myeloid leukemia].
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.
Female↗
Mother-to-child transmission of HTLV-1.
Transmission of HTLV-I via mother's milk has been confirmed by epidemiological studies and by animal experiments using carrier mother's milk and a marmoset. The prevalence rates of HTLV-I carriers in children born of carrier mothers in endemic areas and ATL families were higher than in three control groups of young people. Also, the prevalence rates of carrier mothers who were traced from previously identified carrier children in three groups (two endemic areas and ATL family members) were extremely high. When HTLV-I antigen-positive lymphocytes were detected in carrier mother's milk, the child infection rate was higher than in the cases where antigen-positive cells could not be detected in mother's milk. The number of infected cells present in carrier mother's milk was calculated and the volume of milk given to the baby from delivery to weaning was estimated. Then, an equivalent amount of carrier mother's milk was inoculated into a marmoset orally and this marmoset seroconverted 2.5 months after the inoculation. A campaign to stop carrier mothers from giving their breast milk to their babies has been started in Nagasaki. So far, this trial has been shown to be successful in the prevention of mother-to-child infection.
Adolescent↗
Appearance time of leukemic cells with t(8;21) in bone marrow.
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.
Adult↗
Cytogenetic studies of human T-cell leukemia virus type I carriers. A family study.
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.
Adult↗
Rearrangements in the human T-cell-receptor alpha-chain locus in patients with adult T-cell leukemia carrying translocations involving chromosome 14q11.
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.
Chromosome Mapping↗
Evidence for neoplasia in "pseudolymphoma" of lung.
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Adult↗
Apparently beneficial effect of low to intermediate doses of A-bomb radiation on human lifespan.
Among about 100,000 A-bomb survivors registered at Nagasaki University School of Medicine, 290 male subjects exposed to 50-149 cGy showed significantly lower mortality from non-cancerous diseases than age-matched unexposed males. This was deduced from the fitting of a U-shaped dose-response relationship. Reasons for this effect in males, but not in females, are discussed with reference to selection of individuals and to hormesis.
Dose-Response Relationship, Radiation↗
Survey of anti-human T-cell leukemia virus type I antibody in family members of patients with adult T-cell leukemia.
To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30-39 and the 40-49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out of 63 children with an ATL mother were seropositive. This difference was statistically significant (P less than 0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.
Adult↗
Serum Gc, Hp and alpha 2HS phenotypes in human T-lymphotropic leukemia virus type I infection.
The serum Gc, Hp and alpha 2HS phenotypes were examined in 64 subjects known to have the human T-lymphotropic leukemia virus type I (HTLV-I) infection and in 60 uninfected subjects. There were no significant differences in the distributions of Gc, Hp and alpha 2HS phenotype and allele frequencies between any grouping of HTLV-I-infected subjects and the controls. No association between the Gc, Hp and alpha 2HS genotypes and susceptibility to adult T-cell leukemia was found.
Blood Proteins↗
16;21 translocation in acute nonlymphocytic leukemia with abnormal eosinophils: a unique subtype.
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.
Adult↗
An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.
An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.
Adolescent↗
[Donath-Landsteiner antibody of the IgM class with anti-I specificity and possible efficacy of azathioprine therapy in paroxysmal cold hemoglobinuria: a case report].
In October 1988, a 72-year-old man was admitted to Nagasaki Prefectural Shimabara Onsen Hospital because of hemoglobinuria on exposure to cold. On admission, the laboratory data were Hb 9.1 g/dl, LDH 2,337 U/L, and haptoglobin less than 6 mg/dl. The Donath-Landsteiner (DL) test was positive and serological tests for syphilis were negative. Anti-Coxsackie virus type A9 antibody titer was elevated. Accordingly, he was diagnosed as having paroxysmal cold hemoglobinuria (PCH) associated with viral infection. The DL antibody proved to be of the IgM class having anti-I specificity. The patient was treated unsuccessfully with prednisolone, but hemolysis was improved after azathioprine (AZP) therapy. PCH patients with DL antibody of the IgM class exhibiting anti-I specificity are very rare and only two patients including the present case have been reported in Japan. There has been no report on the efficacy of AZP in PCH, but our study suggests that AZP may have a potential therapeutic effect in some PCH patients.
Aged↗