We have recently demonstrated that human promyelocytic leukemia cell line HL-60 cells expressed distinct glycosphingolipid (GSL) profiles, depending not only on differentiation-stages but also on differentiation-directions. A remarkable increase of an acidic GSL (ganglioside GM3), with a concurrent marked decrease of ceramide dihexoside (the precurnor molecule of GM3), was observed in the process of monocyte-macrophage-lineage differantiation induced with 12-0 tetradecanoyl phorbol-13-acetate (TPA) whereas ganglioside molecular species having longer neolacto-type oligosaccharide-moieties significantly increased during the myeloid (granulocytic) differentiation.
In the present experiment we have tested whether such an increased GSL molecule exhibits any physiological functions in the cell differentiathon processes. HL-60 cells were subcultured and maintained in serum-free media. When the cells were treated with ganglioside GM3 (50nmol/ml ) highly-purified from erythrocyte ghosts, their maturation of monocytic lineage was observed with a simultaneous complete growth-inhibition. Higher ganglio-type gangliosides such as ganglioside GM1, GD1a and GT1b gave no activity on the monocytic differentiation, and instead, showed stimulatory actions on the growth of HL-60 cells in the serum-free culture. Interestingly, in contrast, HL-60 cells were induced to differentiate morphologically and functionally along myeloid lineage when they were treated with neolacto-type gangliosides, which were purified from neutrophils in the chronic phase of chronic myelogenous leukemia.
The present results indicate that ganglioside molecular species specifically increased during a particular lineage of hemopoietic cell differentiation might play, in turn, important physiological roles in the differentiation-induction into the proper cell lineage, and that the sugar-moieties of gangliosides is intimately relevant to the determination of differentiation-directions of hemopoietic cells in addition to the prerequisite presence of membranophilic moieties.

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Immunophenotypic and molecular genetical examinations were performed to 129 patients with acute lymphoblastic leukemia (ALL)/peroxidase (POX) negative acute leukemia. On the basis of phenotypes of leukemia cells, 30 cases were diagnosed as T-cell ALL (T-ALL), 5 as B-cell ALL (B-ALL), 63 as common-ALL (c-ALL), and 31 as acute unclassified leukemia (AUL). AUL cells, which were defined by negative for T-cell antigens, B-cell antigens, c-ALL antigen (CALLA), and POX, were classified into myeloid antigen negative group or positive group. AUL with myeloid antigens were not always considered as myeloid leukemia because of expression of terminal deoxynucleotidyl transferase in some cases.
Genotypes of ALL cells tested by DNA probes for Ig heavy chain (IgH) genes and T-cell receptor (Tc-R) β chain genes also showed that ALL cells consisted of the heterogenous populations. Although most of T-ALL and c-ALL cells had the rearranged Tc-R genes and IgH genes respectively, the simultaneous rearrangements of these two genes (dual genotype) were found in 2T-ALL and 4c-ALL cases. The 18 tested AUL cases were subclassified into 3 major categories; whole germline genotype case (8/18), IgH rearranged genotype case (7/18), and dual genotype case (3/18). Two AUL cases with dual genotype also expressed myeloid antigens, even though one of them had the rearranged Ig light chain genes.
Our results showed that even the genetical examination using as a tool for simple lineage determination was not enough to identify the precise origin of ALL cells, especially AUL cells. ALL cells can be regarded as originating from normal immature cells close to a stem cell stage or bifurcation site for lymphoid and myeloid differentiation. In this sense, a genotype-discordant genotype like the dual genotype and a phenotype-discordant genotype like the Ig rearranged and dual genotype in myeloid antigen positive AUL cells might be thought to represent stochastic differentiation nature of normal stem cells.

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1. Surface markers of the neoplastic cells in patients with hairy cell leukemia were studied. Hairy cells (HC) expressed surface IgG (SIgG) and reacted with Leu M5 monoclonal antibody (αLeu M5) and a rabbit anti-HC serum (αHC-M), which has cross-reactivity to mature granulocytes in CML but does not react with any other leukemic cells. Cytologic and cytochemical studies of normal peripheral blood B lymphcytes showed that most of SIgG⁺ lymphcytes had cytoplasmic processes similar to those on HC and contained tartrate-resistant acid phosphatase activity. Furthermore, many SIgG⁺ lymphocytes reacted with αLeu M5. The reaction pattern of αLeu M5 and αHC-M with normal lymphocytes was different from each other, however, B1⁺, Leu M5⁺ lymphocytes and HC-M⁺ lymphocytes showed a similar distribution among lymphoid tissues; they were found in a very small portion of mononuclear cells from peripheral blood and lymph node, and in a relatively higher proportion of spleen cells.
2. TPA-treatment of the cells in most B cell leukemia samples induced morphologic changes into immunoblastoid and plasmacytoid cells, and Ig production. In contrast, TPA-treatment of HC did not induce a morphologic change into plasmacytoid cells and Ig production, but induced a different morphologic change (Spread). A small portion of normal B cells also spread by cultute with TPA. Cytoplasmic Ig (CIg) was not detected in the majority of the normal spread cells, and most of CIg-positive cells had the appearance of plasmacytoid cells. These findings suggest that HC and other leukemic B cells may involve defferent B cell linages.
3. Conditioned medium prepared from HC culture (HC-CM) inhibited growth of CFU-C and CFU-E. HC-CM had no effect on BFU-E growth. Fractionation study of HC-CM by high pressure liquid chromatography showed that the main inhibitory activity was reside in fractions corresponding to a mean MW of 6000. The inhibitory activity was not detected in CLL-CM and may explain severe cytopemia in hairy cell leukemia.

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Prostglandin production (TXB₂, PGE₂ and 6-keto-PGF₁ α) by peripheral blood mononuclear cells (MNC), adherent cells (AC), nonphagocytic cells (NPC), bone marrow mononuclear cells (BMMNC) and bone marrow nonadherent cells (BMNAC) was evaluated in 60 normal subjects, 26 patients with acute myelocytic leukemia (AML), 10 patients with acute lymphocytic leukemia (ALL) and 21 patients with myelodysplastic syndrome (MDS). Prostaglandin (PG) prodution by MNC and AC in AML and ALL patients was makedly decreased (<1/5 of normal subjects) and that in MDS patients was moderately decreased (1/2∼1/3 of normal subjects). Since PG production level of MNC and AC in patients with acute leukemia (AL) was inversely correlated to the percentage of peripheral blood blast cells, it was suggested that blast cells may suppress the PG production of monocytes in AL patients. PG production by BMMNC in AL patients was decreased and that in MDS patients was normal. However, in patients with AL, no relationship was observed between PGE₂ production level of BMMNC and peripheral blood pictures (Hb levels, leukocyte counts, absolute neutrophil numbers and absolute reticulocyte numbers). As observed in normal subjects, in AL patients, PG production by NPC and BMNAC in which blast cells were enriched and monocytes-macrophages were depleted, was markedly decreased, when compared to MNC and BMMNC. This result suggested that blast cells of AL may not produce PGs.

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We have examined the regulatory effects of human leukemia cells on hematopoietic colony formation (CFU-c). Only M4 and M5 cells produced detectable CSF in their cultured conditioned medium. Molecular weight of this activities was equarl in each cases (27Kd), and was different from that of normal monocyte derived CSF (21Kd). M1, M2 and M3 leukemia cells were induced to CSF producing monocytes by TPA, and many myeloid cell lines were also induced to CSF production by TPA. From these observations, CSF production is one of reliable markers of monocytic differentiation, and leukemic monocytes may produce CSF which affect normal hematopoiesis and leukemia cell proliferation. The other regulatory effect i.e. leukemia cell derived inhibitory activities was studied in the lysate of leukemia cell lines. Almost all myeloid cell lines markedly inhibited colony growth, though, small inhibition was observed by addition of lymphoid cells.
These stimulating and inhibitory activities of leukemia cells should modify their phathophysiology.

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Autonomous nature of malignant cells has been known for many years; that is, they require fewer exogenous growth factors for multiplication than do their normal counterparts. To examine whether human leukemia cells (K-562) can proliferate without exogenous growth factors, longterm cultivation of the cells was carried out in a protein-free chemically defined medium. By the stepwise decreases in the fetal bovine serum concentrations, continuous growth of K-562 cells has been established in a protein-free midium. The cells, designated as K-562Tl, have been well propagated for these six years without exogenous growth factors. The autonomous nature of K-562Tl cells may support the hypothesis that cancer cells produce and respond to their own growth factors and consequently proliferate independently through autocrine secretion. An autocrine growth factor was found in supernatants of K-562Tl cells. The factor designated as leukemia-derived growth factor (LGF) stimulated the proliferation of various human leukemia cells, including myeloid, erythroid, lymphoid, and myeloma cells. In the presence of this factor, these leukemia cells were able to proliferate continuously in a proteinfree medium. These observations led to the speculation that elucidation of the factor that contributed to the independence of K-562Tl cells might shed light on the problem of autonomous nature of malignant cells. In this report, we describe purification and molecular characterization of LGF. LGF was purified to apparent homogeneity from conditioned medium of K-562Tl cells. The purification involved sequential QAE-Sephadex chromatography, gel filtration, and Mono S fast protein liquid chromatography. The purified factor showed a single protein band on sodium dodecyl sulfate polyacrylamide gel electrophoresis, by the silver staining technique. Its amino-terminal sequence was determined as Met-Gln-Ile-Phe-Val-Lys-Thr-Leu-Thr-Gly-Lys-Thr-Leu-Glu-Val-Glu-Pro-X-Asp-X-Ile-X-Asn-Val-Lys-Ala-X-Ile-. The amine-terminal sequence and molecular size indicate that the structure of LGF is different from other known growth factors. Interestingly, the amino-terminal sequence of LGF was found to be identical to the sequence of ubiquitin, a part of nuclear protein A24. However, ubiquitin (Mr.=8,600) purified from bovine thymus did not show any growth-promoting activity against human leukemia cells tested. The results suggest that LGF is a unique autocrine growth factor that shares a common amino-terminal amino acid sequence with ubiquitin. Ubiquitin has been implicated in a variety of cellular functions both in the nucleus and in cytoplasm. However, little is known about the specific functions of ubiquitin systems. Our observations that an autocrine growth factor, LGF, contains a common amino-terminal amino acid sequence with ubiquitin may provide a clue for better understanding of the specific functions and if any, the association of ubiquitin systems and cell proliferation.

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Leukemic cells obtained from peripheral blood of a patient with chronic myelogenous leukemia in blast crisis and of a patient with acute myelogenous leukemia and a human leukemic cell line K562 contained a transforming growth factor (TGF), which promotes anchorage-dependent BALB/C 3T3 cells to from progressively growing colonies in soft agar. The TGF was heat-and acid-labile, relatively stable to dithiothreitol treatment and inactivated by pronase treatment. When subjected to gel filtration on a column of Sephadex G100, TGF activity was eluted in fractions corresponding to an apparent molecular weight of 20,000. This TGF did not compete with epidermal growth factor for receptor binding.

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Acute myelofibrosis (AMF) is characterized by rapid onset of pancytopenia, extensive bone marrow fibrosis, and absence of hepatosplenomegaly. Studies were made on seven cases with AMF. Blastic cells including megakaryoblasts found in the specimens prepared from biopsied bone marrow ranged from 0.8 to 16.4%, and two and five cases corresponded to RA and RAEB, respectively, according to the FAB classification. Five cases out of the seven transformed into M1, M4, M5 and acute megakaryoblastic leukemia (AMgL) in three to seven months.
Since AMF was almost the same as chronic idiopathic myelofibrosis on biopsied bone marrow findings, the lesion was considered to be myeloproliferative disorder of acute type resulting from abnomality of the multipotent stem cell.
The fact that blastic cells emerged in the bone marrow in various degrees can be eluciated as follows; the hematological change would occur rapidly in AMF and show various hematological patterns corresponding to pure AMF, RAEB, RAEB-T or acute leukemia according to the stage of the disorder, and clonal evolution was induced to various directions, developing various types of leukemia corresponding to the evolutions. Finally, dissimilarity between AMF and AMgL is discussed. Though there were striking similarities between AMF and AMgL, we concluded that the two disorders appeared to be nonidentical from our experience.

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Clinical observation was made of 38 patients with myelodysplastic syndromes (MDS), including 6 refractory anemia (PA), 3 sideroblastic anemia (SA), 10 refractory anemia with excess of blasts (RAEB), 9 RAEB in transformation (RAEB in T), and 10 chronic myelomonocytic leukemia (CMMOL) and the following findings were obtained. Almost all patients were elder in age and CMMOL was older than RA (p<0.05) and males outnumbered females except SA. MDS patients tended to evolve in these three patterns
1. RA (SA)→RAEB→RAEB in T→AML
2. RA→RAEB→CMMoL (acceralated phase; AP)→(blastic crisis; BC)
3. CMMoL (chronic phase; CP)→(AP)→(BC)
Evolution of pattern 1, 2, 3 was observed within about 4 years but these intervals were various, and this variety was thought to depend on the time when MDS was found. Among RAEB and RAEB in T, three patients achieved CR by intensive chemotherapy, but other MDS patients died of infection or bleeding. We couldn't prevent their evolution of diseases except 2 RA patients who responded to steroid. Once MDS patients evolved AML or CMMoL (AP) they were not induced to CR nor CP, in spite of any chemotherapy.

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We evaluated a new parameter designated lobularity index (L.I.) in a new blood cell counter, H-1.
(1) The L.I. values of the patients with leukocytosis showing or not showing left shift of nuclear lobularity were studied. L.I. values of the cases with left shift had no significant difference from those of the cases without left shift.
(2) Although no correlation was shown between L.I. values and % band form on the May-Grünwald-Giemsa stained films, a high correlation was shown between the L.I. value and total percentage of band form, lymphocyte and monocyte, and a better one between the L.I. value and total percentage of lymphocyte and monocyte.
(3) Normal value of L.I. is defined by the counter as above 1.9, and a flagging mark is shown outside the value. Incidence of flagging mark of false positive was 43%, and that of false negative was 41% comparing with eye count method.
From these results, we concluded that L.I. values shown by H-1 did not reflect the left shift of nucleus which was observed in leukocytosis in a case of acute inflammation.

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Nine children under 15 years of age with diffuse large cell lymphoma were treated between 1972 and 1984. According to the Ann Arbor classification, 3 cases were in stage I, 3 in stage II and 3 in stage IV. Seven of 9 cases were treated with the modified protocol of original report by Aur which did not include either anthracycline or prophylaxis for central nervous system (CNS) disease. Two other cases (Stage I and II) were treated with the modified LSA₂-L₂ psotocol. Up to the end of August, 1986 (median follow-up of 6 years), two relapses have occurred. A 2 year old girl, diagnosed as immunoblastic type, Stage IV, developed CNS disease 3 months after diagnosis and died at 11 months. Another 7 yea-old boy who had Stage II disease of the left neck origin, developed relapse at contralateral side of the neck at 92 months (68 months after cessation of the treatment). After removal of recurrent tumor and short course of chemotherapy, he refused further treatment, but remains free of disease 153 months after presentation. Seven other cases remain free of disease between 21 to 143 months after diagnosis.
Failure-free survival in 9 cases are 89% at 60 months, and 59% at 91 months. Overall survival is 89%. The results is significantly better than that for other types of non-Hodgkin's lymphoma (lymphoblastic and small non-cleaved) treated during the same period of time at our institutions. From our experience, although the number of cases is small, it appears that diffuse large cell lymphoma in children could be controlled with less toxic therapeutic regimen except immunoblastic type.

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The inhibitory action of methotrexate (MTX) on deoxyuridine (UdR) incorporation and the rescue effect of folate derivatives for acute leukemia cells were investigated and compared with those of normal bone marrow cells. UdR incorporation was suppressed most remarkably in acute leukemia cells over a wide concentration range of MTX. The reduced folate derivatives (5-formyltetrahydrofolate, 5-methyltetrahydrofolate) reversed the suppressed UdR incorporation more efficiently than the unreduced folates (pteroylgulutamic acid, dihydrofolate). The extent of reversion was less significant in acute leukemia cells when compared with bone marrow cells either from hematologically normal subjects or from patients with normoblastic hyperplasia.
These results indicate that the acute leukemia cells possess elevated sensitivity to MTX and that they are rescured by folates with less efficiency. These observation may be relevant to the known clinical usefulness of MTX obtained in combination with rescue by a reduced folate in treatment of acute leukemia.

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From 1981 to 1983, 131 previously untreated patients with childhood acute lymphoblastic leukemia were stratified in the standard risk group and were entered on this protocol S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by the treatment with prednisone (PRD) and vincristine (VCR) or vindesine (VDS). There was no significant difference between VCR and VDS. After preventive central nervous system (CNS) therapy uniformly including 18Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were randomized to receive a maintenance chemotherapy of Regimen A or Regimen B. The Regimen A consisted of MTX 225mg/m² i.v. push alternating at two week-interval VCR 2.0mg/m²×1, PRD 120mg/m²/d×5 and 6-mercaptopurine (6MP) 175mg/m²/d×5. The Regimen B consisted of daily 6MP 50mg/m² and MTX 20mg/m² p.o. weekly combined with pulses of VCR and PRD every four weeks. As a late intensification therapy (LIT), five courses of high-dose (2,000mg/m² i.v.) MTX with leukovorin rescue were administered to all the patients in continuous complete remission (CCR) for more than two years. Sixty and 55 patients were registered in Regimen A and B, respectively. The CCR rates in regimen A and B were 79.2%±5.4% (mean±SE) and 69.5%±6.4% at 3 years, 74.5±6.0% and 51.6%±8.0% (p<0.05) at 4 years, and 74.5%±6.0% and 45.1±9.3% at 5 years (p<0.01), respectively. CNS and testicular relapses appeared to be increased in the Regimen B after 3 years duration of CCR. The LIT with high-dose MTX showed no important effect on the duration of CCR. We conclude that the intermittent pulses of 6MP and MTX may be more effective than the continuous administration of these drugs for a maintenance chemotherapy.

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Since the first report by Ueshima et al. concerning the chromosome of ATL, many studies have been reported. The 14q+marker chromosome, often found in B-cell malignancies has been also found in ATL. Sadamori et al. have reported recently the break points at 14q11—13 in ATL. We present the cytogenetic findings in 16 patients with ATL seen in Northern Kyushu island; nine were patients with acute type leukemia, one with crisis type, one with chronic type and five with lymphoma type. The serum antibody for HTLV-1 (ATLA) was positive in all patients and the phenotype of ATL cells were ERFC⁺, OKT3⁺, OKT4⁺, OKT6^-, OKT8^-, OKT10⁺, OKIal^+,- and Tac⁺. abnormal findings of chromosomes were observed in 15 patients. Thirteen patients were in near diploid range. One patient was in triploid range and one patient was in tetraploid range. The polyploid karyotypes were found only in lymphoma type patients with ATL. Trisomy 3 and trisomy 7 were observed each in 3 patients. The most frequent abnormal rearrangement was observed in the long arm of chromosome 6. Recurrent break points were 6q15 and 6q21 which had been previously reported by Miyamoto et al. The abnormal rearrangements involving 6q15 and 6q21 band were observed in 4 patients in this series.

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Clinical and immunological studies were performed in 2 cases with chronic active Epstein-Barr (EB) virus infection. High titer of VCA·IgG and EA·DR·IgG antibodies against EB virus, prominent hepatosplenomegaly and lymphadenopathy were persistently observed.
Transient thrombocytopenia was developed in both cases and hemolytic anemia was developed in one case.
The highest EB virus antibody titer was 1:640 and 1:5120 in VCA·IgG, 1:80 and 1:640 in EA·DR·IgG, and less than 1:10 and 1:160 in EBNA. VCA·IgM antibody was less than 1:10 in both cases.
OKT4/OKT8 ratio was lower than 1.0 during thrombocytopenia stage in one case and elevated OKT10⁺ lymphocytes and OKIAl⁺ lymphocytes was observed in both two cases.
Natural killer (NK) cell activity and EB virus specific cytotoxic T lymphocyte (EBV-CTL) activity were low in both two cases, and these defective killer cell activities were not enhanced to normal range even after stimulation by interferon α, interferon γ, OK-432 or interleukin 2 in vitro. Lymphokine activated killer (LAK) activity was also weak in both two cases, indicating that defects of these killer cell activity provoke persistency of EB virus, and stir up various immunodefficiency.

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In order to clarify the immune response in adult T cell leukemiea (ATL), Epstin-Barr virus (EBV)-specific antibody titers in sera from 35 patients with ATL and 128 healthy controls were measured by an immunofluorecence method. EBV is an infectious agent ubiqitous throughout the world and is koown to be latent lifelong. When the immune competence in host is depressed, EBV may be reactivated, resulting in a change of EBV-specific antibody titers.
Our findings showed that the mean titers of EBV capsid antigen (VCA)-IgG antibody and the positive rate of early antigen (EA)-IgG antibody in sera of patients with smoldering type ATL were higher than in sera of healthy controls. And these antibody titers increased with the stage of ATL. However, no differences were seen in antibody titers to EBV-associated nuclear antigen (EBNA) between the ATL patients and the controls.
These results suggest that there may be an abnormality in the immune competence in persons infected with human T cell lymphotropic virus type-1 (HTLV-1).

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Because hairy cell leukemia (HCL) in the Japanese is not only rare but shows several atypicalities in the clinical and immunological features, the Japanese HCL is considered itself a variant of HCL. This study on Japanese HCL concerns with the aspect of possible retroviral involvement in view of the endemic prevalence of HTLV-I-associated ATL in Japan as well as the recent isolation of HTLV-II from another patient again with the T-cell variant of HCL.
Results of this study have demonstrated presence of antibodies to the structural peptides of HTLV-I and/or HTLV-II in sera from all 11 HCL patients surveyed. However, the antibody reaction in each case did not appear strong enough to derive from active infection by HTLV-I or HTLV-II. Instead, the results raised a possibility of a role by an unknown retrovirus capable of cross-reaction with HTLV-I and/or HTLV-II.

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Patient was a 30 years old man who was admitted because of anemia. Examination revealed a slight jaundice with splenomegaly extending 5cm below the left costal margin. Blood counts were RBC 271×10⁴/μl, Hb 10.4g/dl, Ht 28%, MCV 103.3μ³, reticulocyte 32‰, WBC 8900/μl and platelet count 17.4×10⁴/μl.
Aniso-poikilocytosis and macrocytosis were observed in peripheral blood. Severe erythroid hyperplasia with bi or multinucleation and Feulgen positive internuclear chromatin bridge were observed in his bone marrow aspirate. At the ultrastructural level, uneven chromatin condensation with sponge like appearance and absence of nuclear envelope with cytoplasmic organelles in nuclear area were also ovserved.
Ferrokinetic studies using ⁵⁹Fe revealed ineffective erythropoiesis. The ⁵¹Cr red cell survival (T ½) wfs 19 days. His erythrocytes showed negative acidified serum test and they were not agglutinated by anti-I or anti-i sera.
All data seem to justify the diagnosis of CDA type I. Drug therapy including pyridoxin, vitamin B₁₂ and folic acid was not effective. Family studies showed the consanguinity of his parents.

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Two cases of Aeromonas septicemia with acute myelogenous leukemia are presented. Both cases were complicated with Aeromonas septicemia when peripheral leukocytes were markedly decreased, and accompanied by abdominal pain, diarrhea and disseminated intravascular coagulation syndrome. Inspite of administration of antibiotic agents which were active against the bacteria, patients died within 2 weeks.
Our cases were fatal as cases reported in the literature in whom Aeromonas septicemia developed in neutropenic states of less than 500/μl. As Aeromonas is found in water and soil widely, and it is resistent to chlorination, Aeromonas infection must be checked out more carefully during the treatment of acute leukemia and other neutropenic states, although it is relatively rare.

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A 47-year-old woman underwent an operation of extended simple hysterectomy for uterine cervical carcinoma (Stage Ia) in February 1979. The patient felt very languid by May 10, 1980. Thereafter, she noticed a tumor in her left anterior chest wall. As hemorrhagic diathesis appeared, she was admitted to the Akita University Hospital at May 27, 1980. She was diagnosed as acute plasma cell leukemia (IgG-κ) and was treated with melphalan and prednisolone. The right pleural effusion, which contained plasma cells, was revealed on the day following the admission. Bloody effusion was taken off by thoracentesis six times (total 8,900ml), nevertheless, she died of respiratory failure at June 11, 1980. By the postmortem examination, the mechanism of pleural effusion was regarded as the pleural infiltration of plasma cells from the extra-medurally plasmacytoma in the posterior portion of sternum.

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A 52-year old man presented with lumbago, proteinuria and anemia. A diagnosis of Bence Jones protein (BJP) λ type multiple myeloma was made because of increased atypical plasma cells in the bone marrow, BJP in the urine, decreased immunoglobulins and osteoporotic changes in the bone. He received combination chemotherapy (VENP), but the remission was not gained. Systemic amyloidosis involving the gastrointestinal tract and joints caused various symptomes such as hematemesis, melena, arthralgia and carpal tunnel syndrome. The amyloid material was histochemically proved.

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A 77-years-old female had been treated for refractory anemia for 3 years before she was admitted to our hospital with a complaint of high fever which persisted for one month. The peripheral blood showed Hb 6.3 g/dl, RBC 223×10⁴/μl, thrombocytes 45.3×10⁴/μl with occasional giant forms, and WBC 36200/μl with 1% promyelocytes, 2% myelocytes, 4% metamyelocytes, 43% band forms, 38% segmented neutrophils and 9% monocytoid cells. Bone marrow aspiration revealed hypercellularity with a marked increase of myelomonocytic series including 4.8% of blastic cells.
Urine contained many neurtrophils and bacilli. CRP was strongly positive. She was given antibiotics and after one week her fever subsided. Hematological findings about one month after pyretolysis were as folloes; Hb 8.0g/dl, RBC 292×10⁴μl, thrombocytes 48.6×10⁴/μl, and WBC 9300/μl with 2% myeloblasts, 2% promyelocytes and myelocytes, 1% metamyelocytes, 24% band forms, 18% neutrophils and 33% monocytoic cells. Bone marrow examination revealed hyperplasia not only of myelomonocytic series but also of megakaryocytes. Cytogenetic studies of bone marrow showed 46, XX. The in vitro colony counts of CFU-C from the bone marrow were within nomal limits.
Hematological findings and colony formation in our patient were similar to those found in CML patients. The fact that our patient showed leukocytosis, mainly consisting of nomal neutrophils, during bacterial infection is clinically important, because this suggests the presence of a nomal clone having ability to differentiate by infection in stem cells of CMMoL patients.

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We perfomed morphologic, biochemical, and functional studies on the platelets from two subjects in a single family with May-Hegglin anomaly.
Analysis of the platelets by Sysmex E-5000 showed that mean platelet volume of the propositus and his mother was 2.4 and 2.5 times larger than those of normal individuals, and that platelet-large cell ratio was 74.7 and 77.8%, respectively. Ultrastructural studies, however, revealed normal size and distribution of the platelet granules.
The concentration of granule-bound substances, such as beta-thromboglobulin, 5-hydroxytryptamine, platelet factor-4, and ATP, was significantly elevated in the platelets of the subjects.
The platelets of the subjects showed both sufficient aggregation and release of significant amounts of ATP in the presence of either ADP, collagen or ristocetin, while aggregation was not seen and only ristocetin induced the ATP-release when the same concentration of platelets from normal individuals was examined.
These results indicated that total circulating platelet mass and the function are in the similar levels to those of normal individuals, although thrombocytopenia exists in this disorder.

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A case with type 1 Gaucher's disease accompanied with myelodysplastic syndrome (RAEB) is reported.
Fifty-seven years old female was referred to our hospital because of pancytopenia in March 1984. She was found to have hepatomegaly and marked splenomegaly, but any neurological findings were not seen. Bone marrow biopsy revealed accumulation of large cells (Gaucher's cell) and myelodysplastic findings. The β-qlucosidase activity of her peripheral leukocyte was decreased to 37% of normal value and the neutrophiles alkaline phosphatase score (NAP) was low. She was diagnosted as type 1 Gaucher's disease accompanyed with refractory anemia with excess of blast. She underwent splenectomy for progressive pancytopenia. But with effect, she died of pneumonia. Histochemical staining of bone marrow cells using a battery of POD-labelled lectins proved no difference of staining pattern between Gaucher's cells in this case and Psudo-Gaucher's cells in patients with CML. And also, we recognized the tendency that β-glucosidase activity of peripheral leukocytes in patients with CML was raised.

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A 51-year-old man was admitted to the hospital because of fatigue, dizziness and palpitation on October 12, 1984. The physical examination revealed pallor. There was slight hepatosplenomegaly. RBC was 216×10⁴/μl, Hb 7.7g/dl, and WBC was 8200/μl with 45% myeloblasts. Platelet count was 5.1×10⁴/μl. Neutrophil alkaline phosphatase score was 82 (normal range 170-285). The bone marrow contained 54.6% blasts, and was compatible with the M2 type of acute myeloid leukemia. The blasts were histochemically positive for peroxidase and naphthol AS-D chloroacetate esterase, but negative for α-naphthyl butyrate esterase. Bone marrow chromosomal analyses by Q-banding revealed 46, XY, t (7; 11) (p15; p15). Treatment with BHAC, daunorubicin, 6MP, and prednisolone resulted in complete remission. He has survived over 2 years.
This translocation has not been previously reported.

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Two patients with acute myelocytic leukemia developed multiple liver abscesses which was confirmed by CT after chemotherapy. A 27-years-old woman was treated by various anti-bacterial and anti-fungal agents for a prolonged period but a spiking fever and right hypochondralgia continued. With oral norfloxacin (NFLX), symptoms and abnormal data were resolved and she was discharged.
Another patient, a 61-years-old women, also suffered from high fever in spite of intensive antibiotic therapy incruding latamoxef. Combination treatment with NFLX and latamoxef induced a rapid resolution of her liver abscesses. They were followed on NFLX alone in the outpatient clinic. NFLX has a strong, broad-spectrum antimicrobial activity and attains a high concentration in the liver. Synergistic action of NFLX and a β-lactam agent has ben reported.
Furthermore, NFLX can be administrated orally. Therefore, NFLX appears to be a drug of choice for the treatment of liver abscesses not only because of its effectiveness but also of its low cost.

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We are presenting two cases of childhood acute lymphoblastic leukemia with translocation (4; 11) who were first diagnosed under four months old. Leukemia cells from peripheral blood and bone marrow in the first case were classified into L₁ ALL according to FAB classification. Cytochemical stainings were peroxidase negative, PAS weakly positive and non-specific esterase negative.
Immunologic marker studies showed J₅ (CD-10) negative, I₂ (antiHLA-DR) positive, B₄ (CD-19) positive and negative for myeloid markers.
Cytogenetic study was perfomed at diagnosis both from peripheral blood and bone marrow cells and all the metaphases obtained showed 48 XXX, t (4; 11), (q21; q23), +6. The patient is now in continuous complete remission for eight months after diagnosis.
The second case was also classified as L₁ ALL with negative staining for peroxidase and immunologic marker study was done only for J₅ with 46.3% positivity. Cytogenetic study at diagosis showed 46XX normal female karyotype. Seventeen months after continuous complete remission the patient relapsed as ovarian tumor.
Cytogenetic study showed 46XX. t (4; 11) (q21; q23), 15q^-.
Leukemia with translocation (4; 11) seems to be not so rare for early infants and the precise features of the leukemic cells should be evaluated further.

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A rare case of biclonal gammopathy with IgD-λ and IgA-κ in serum and κ type and λ type Bence Jones proteins in urine is described.
A 79-year-old female was admitted to the hospital because of an anemia. On examination the edge of the liver was palpable 4 cm below the right costal margin. Urine was positive for Bence Jones protein. The hematocrit was 21.7 per cent, white cell count 2,800/μl and platelet count 226,000/μl. The urea nitrogen was 35mg/dl, creatinine 4.8mg/dl and total protein 7.7g/dl. Electrophoresis of the serum on cellulose acetate showed the presence of a slight abnormal peak in γ region. On quantitative studies IgG was 332mg/dl, IgA 279mg/dl, IgM 20>mg/dl and IgD 640mg/dl. Immunoelectrophoresis showed the existence of IgD-λ and IgA-κ M proteins in serum and light chain κ and λ Bence Jones proteins in urine. A bone marrow aspirate contained 89.8 per cent atypical plasma cells. Bone marrow sample was stained with anti-δ and anti-α chain antibodies to investigate the origin of two M components and the presence of separate cell populations was disclosed. Furthermore, anti-idiotypic antisera to each isolated protein were prepared in rabbits. No common individual antigenic determinants were found in these two proteins.
The diagnosis of this patient was supposed to be double myeloma or IgD myeloma associated with IgA type bengn monoclonal gammopathy.

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A 47-year-old Japanese female was admitted because of general malaise, systemic lymphadenopathy, hepatomegaly and skin lesions in May, 1982. The white blood cell count was 152,000/μl with 91.5% of abnormal lymphocytes. Those had nuclear irregularity such as convolution and segmentation. The cell surface phenotype of abnormal lymphocytes defined by monoclonal antibodies was OKT3+, OKT4+ and OKT8-. The serum lactic dehydrogenase value was 1,075 mU/ml, serum calcium 13.7mg/dl, and the titer of anti-ATLA antibody in serum ×80. Marked proliferation of abnormal lymphocytes was also observed in pleural exsudates. Therefore the diagnosis of acute adult T cell leukemia (ATL) was made. She received combined chemotherapy (vincristine, cyclophosphamide, prednisolone, adriamycin, ACNU, methotrexate, L-asparaginase and/or adenocine arabinoside). In September 1982, her condition improved and abnormal lymphocytes could not be morphologically found in her peripheral blood. Until August 1985, she received consolidation therapy (vincristine, cyclophosphamide, prednisolone, aclarubicin, bephenoyl ara-C or high-dose methotrexate) every three months. In July 1986, the proviral DNA of human T cell leukemia virus type 1 was examined in the peripheral blood mononuclear cells using Southern blotting method. Although cellular DNA was digested with restriction endonucleases (EcoR1, Pst1 and Sac1), the proviral DNA was not detected. Adult T cell leukemia-cell-associated antigen in short-term culture of peripheral blood mononuclear cells could not be also detected. She is presently well without chemotherapy and no abnormal lymphocyte was not observed in the peripheral blood until December, 1986

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A 48-year-old woman suffering from adult T-Cell leukemia (ATL) along with a generalized cytomegalovirus (CMV) infection was reported. The patient had a wide-spread eruption and an increased numbers of leukocytes about 10 years ago, but these findings remained stable without the necessity of treatment until January, 1984 when she was refered to our hospital because of her abrupt splenomegaly and leukocytosis. The laboratory data on admission revealed mild anemia and a leukocyte count of 38,800/μl with 27.4% of the leukemic cells in her peripheral blood. Proviral DNA was demonstrated in the leukemic cells and the ATLA antibody was positive so that a diagnosis of ATL was made. She was effectively treated with VEMP, but started complaining of a remittent fever and cough. The chest X-ray film disclosed interstitial pneumonia. Her dyspnea became aggravated inspite of intensive therapy. She died on the 85th day of hospitalization. An autopsy disclosed that leukemic cells had infiltrated into the systemic organs and that the inclusion bodies due to CMV infection were recognized in the systemic lymph nodes, tonsils, lungs, liver, spleen and kidneys.
Opportunistic infections should always be considered in the treatment of ATL patients even if the leukemic cells were successfully managed, since they may have a secondary immunodeficiency due to an infiltration of leukemic cells in the immune organs and from the repeated use of chemotherapy.

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