Overexpression of the Golgi-localized enzyme alpha-mannosidase IIx in Chinese hamster ovary cells results in the conversion of hexamannosyl-N-acetylchitobiose to tetramannosyl-N-acetylchitobiose in the N-glycan-processing pathway.

Golgi alpha-mannosidase II is an enzyme that processes the intermediate oligosaccharide Gn(1)M(5)Gn(2) to Gn(1)M(3)Gn(2) during biosynthesis of N-glycans. Previously, we isolated a cDNA encoding a protein homologous to alpha-mannosidase II and designated it alpha-mannosidase IIx. Here, we show by immunocytochemistry that alpha-mannosidase IIx resides in the Golgi in HeLa cells. When coexpressed with alpha-mannosidase II, alpha-mannosidase IIx colocalizes with alpha-mannosidase II in COS cells. A protein A fusion of the catalytic domain of alpha-mannosidase IIx hydrolyzes a synthetic substrate, 4-umbelliferyl-alpha-D-mannoside, and this activity is inhibited by swainsonine. [(3)H]glucosamine-labeled Chinese hamster ovary cells overexpressing alpha-mannosidase IIx show a reduction of M(6)Gn(2) and an accumulation of M(4)Gn(2). Structural analysis identified M(4)Gn(2) to be Man alpha 1-->6(Man alpha 1-->2Man alpha 1-->3)Man beta 1-->4GlcNAc beta 1-->4GlcNAc. The results suggest that alpha-mannosidase IIx hydrolyzes two peripheral Man alpha 1-->6 and Man alpha 1-->3 residues from [(Man alpha 1-->6)(Man alpha 1-->3)Man alpha 1-->6](Man alpha 1-->2Man alpha 1-->3)Man beta 1-->4GlcNAc beta 1-->4GlcNAc, during N-glycan processing.

Suppressive effects of swainsonine and N-butyldeoxynojirimycin on human bone marrow neutrophil maturation.

The effects of the N-linked oligosaccharide inhibitors swainsonine and N-butyldeoxynojirimycin (NB-DNJ) on granulopoiesis was investigated using human bone marrow cells in in vitro liquid and agar cultures. The addition of the inhibitors into cultures containing granulocyte colony-stimulating factor (G-CSF) suppressed maturation from myelocytes into mature neutrophils. Swainsonine did not induce apoptosis, but NB-DNJ induced considerable apoptosis, especially in the presence of G-CSF. This result indicated that the decrease of mature neutrophils by swainsonine was not because of cell degeneration. In the case of NB-DNJ, it was thought to be because of both maturation suppression and apoptosis. In a colony-forming unit-granuloid (CFU-G) colony assay, the number of colonies was increased in the presence of the inhibitors, but the morphology of colonies was predominantly compact, or immature. The inhibitors also suppressed the expressions of mRNAs of CCAAT/enhancer binding protein epsilon (C/EBPepsilon) and G-CSF receptor as markers of terminal neutrophil maturation. These findings suggested that the incompleteness of N-linked oligosaccharide leads to the suppression of terminal neutrophil maturation.

Constitutive activation of LIL-Stat in adult T-cell leukemia cells.

The activation status of a recently identified STAT (signal transducers and activators of transcription) factor, LIL-Stat (lipopolysaccharide [LPS]/IL-1-inducible Stat) in adult T-cell leukemia (ATL) cells was investigated by electrophoretic mobility shift assays using nuclear extracts of leukemic cells from 7 patients with ATL and a GAS (gamma interferon activation site)-like element termed LILRE (LPS/IL-1-responsive element), which is found in the human prointerleukin 1beta (IL1B) gene. Spontaneous DNA binding of LIL-Stat was observed in all ATL cells examined. However, in normal human peripheral lymphocytes, DNA binding of LIL-Stat was detected only after stimulation with IL-1. These results demonstrated that LIL-Stat is constitutively activated in ATL cells. Furthermore, our transient transfection studies using LILRE chloramphenicol acetyltransferase (CAT) reporters argue that LIL-Stat in ATL cells functions as a transcriptional activator through binding to the LILRE in the IL1B gene. (Blood. 2000;95:2715-2718)

Adult T-cell leukemia/lymphoma in which the pathohistological diagnosis was identical to that of Ki-1 positive anaplastic large cell lymphoma.

A 65-year-old man developed severe lumbago and a loss of appetite two months before presentation. A computerized tomograph at admission revealed soft tissue masses destroying the Th12, L4 and L5 vertebral bones. We diagnosed the lesions to be metastatic bone tumors, but the primary focus could not be determined. Just after the irradiation treatment, abnormal lymphocytes were detected in the peripheral blood cells. Under the suspicion of adult T-cell leukemia/ lymphoma (ATL), we thus performed a lymph node biopsy. The specimens were histologically composed of Ki-1 positive anaplastic large cell lymphoma (ALCL). The lymphoma cells demonstrated a biclonal integration of HTLV-1 proviral DNA. After 6 cycles of chemotherapy, the patient has demonstrated a partial and favorable remission from ATL.

Human T-cell leukemia virus type I Tax transactivates the promoter of human prointerleukin-1beta gene through association with two transcription factors, nuclear factor-interleukin-6 and Spi-1.

The human T-cell leukemia virus type I (HTLV-I), which infects a wide variety of mammalian cells including monocytes and macrophages, encodes a transactivating protein designated as Tax. We now report that Tax induces the human prointerleukin-1beta (IL1B) gene promoter in monocytic cells. In our transient transfection assays using human THP-1 monocytic cells, a chloramphenicol acetyltransferase (CAT) construct containing the IL1B promoter sequence between positions -131 and +12 showed an approximately 90-fold increase in activity following cotransfection of a Tax expression vector. Moreover, Tax synergized with lipopolysaccharide (LPS) to induce the IL1B promoter activity. Analyses of specific nucleotide substitutions further indicated that the Tax-induced transcriptional activation requires two transcription factor binding motifs within the IL1B promoter; one is a binding site for nuclear factor (NF)-IL6 (CCAAT/enhancer binding protein beta, C/EBP beta), which belongs to the basic region-leucine zipper (bZIP) family and the other for Spi-1 (PU.1), which is an Ets family protein found principally in monocytes, macrophages, and B lymphocytes. In electrophoretic mobility shift assays (EMSA) using in vivo THP-1 nuclear extracts, Tax expression in THP-1 monocytic cells significantly increased binding of the two factors to their target IL1B promoter sequences. However, in contrast to NF-IL6 and Spi-1, DNA binding activity of Oct-1, an ubiquitously expressed octamer-binding protein was not affected by Tax. Additional EMSA using in vitro translated proteins also showed that recombinant Tax enhances DNA binding of both of recombinant NF-IL6 and Spi-1 proteins. These data were supported by our glutathione S-transferase (GST)-pull-down data, which indicated that Tax physically interacts with the two proteins. Based on the results obtained from the present study, we conclude that the IL1B promoter is a Tax-responsive sequence as a result of ability of Tax to induce binding of NF-IL6 and Spi-1 to the IL1B promoter sequence through protein-protein interaction.

Structure and transcriptional regulation of human alpha-mannosidase IIX (alpha-mannosidase II isotype) gene.

Golgi alpha-mannosidase II is a key enzyme of N-glycan processing. Its genetic defect is associated with HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test). We previously cloned cDNAs of human alpha-mannosidase II (alpha-MII) and its isotype, alpha-mannosidase IIX [alpha-MIIX, Misago, M., Liao, Y. F., Eto, S., Mattei. M. G., Moremen. K. W. & Fukuda, M. N. (1995) Proc. Natl Acad. Sci. USA 92, 11766-11770]. Constitutive expressions of alpha-MII and alpha-MIIX mRNA were shown in various human tissues. To investigate the transcriptional regulation of alpha-MIIX gene, we characterized the cosmid clone of 40-kb that includes the 5'-flanking sequence. This clone contains at least eight exons which encode 396 amino acid residues of a total of 1139 amino acid residues of alpha-MIIX. Primer-extension analysis revealed multiple transcription-initiation sites in the range from -70 to -58 relative to the translation-initiation site. No canonical TATA or CAAT boxes were observed, but a (G + C)-rich region was found in close proximity to the transcription-initiation site. To localize the transcriptional regulatory region of this gene, various regions of the 5' sequences were fused to the luciferase gene, and transient-expression assays were conducted in human melanoma G-361 cells. These studies indicated that sequence from -12 to + 11 relative to the most distal 5'-transcription-initiation site was involved in the promoter function. Within this region, the sequence GGGCGT similar to the consensus sequence of the Sp1 binding site, is present at positions -12 to -7. Enhancer activities were found in the region upstream of this site, notably from -4300 to -252. Thus, the alpha-MIIX promoter located in a CpG island is also regulated by upstream elements, indicating the complexity of alpha-MIIX gene expression.

[A clinical evaluation of fluconazole in deep seated fungal infections associated with hematological disorders].

The effectiveness of fluconazole on deep seated fungal infections associated with hematological disorders was evaluated in a multicenter clinical study. The underlying diseases included acute myeloblastic leukemia, acute lymphocytic leukemia, malignant lymphoma, adult T cell leukemia, multiple myeloma and others. Fluconazole (FLCZ) was administrated 100-400 mg/day intravenously or orally to 79 patients with systemic fungal infections complicated with hematological disorders and it was possible to evaluate clinical efficacies in 60 patients. 27 patients were diagnosed as having determinate systemic fungal infections and 33 patients suspected fungal infections. The clinical efficacies were 81.5% (22/27) in patients with diagnosed fungal infections and 57.6% (19/33) in patients with suspected fungal infections. The overall clinical efficacy was 68.3% (41/60). No side effects such as gastrointestinal symptoms, vascular pain and renal dysfunction were observed in this study. As for abnormal laboratory test, transient increases in GOT, GPT, Al-P, LDH, serum Na, Cl and decrease in serum K were observed in 9 patients (11.4%). These results indicated that FLCZ has a high therapeutic efficacy on deep seated fungal infections in patients with hematological disorders.

Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme.

Golgi alpha-mannosidase II (alpha-MII) is an enzyme involved in the processing of N-linked glycans. Using a previously isolated murine cDNA clone as a probe, we have isolated cDNA clones encompassing the human alpha-MII cDNA open reading frame and initiated isolation of human genomic clones. During the isolation of genomic clones, genes related to that encoding alpha-MII were isolated. One such gene was found to encode an isozyme, designated alpha-MIIx. A 5-kb cDNA clone encoding alpha-MIIx was then isolated from a human melanoma cDNA library. However, comparison between alpha-MIIx and alpha-MII cDNAs suggested that the cloned cDNA encodes a truncated polypeptide with 796 amino acid residues, while alpha-MII consists of 1144 amino acid residues. To reevaluate the sequence of alpha-MIIx cDNA, polymerase chain reaction (PCR) was performed with lymphocyte mRNAs. Comparison of the sequence of PCR products with the alpha-MIIx genomic sequence revealed that alternative splicing of the alpha-MIIx transcript can result in an additional transcript encoding a 1139-amino acid polypeptide. Northern analysis showed transcription of alpha-MIIx in various tissues, suggesting that the alpha-MIIx gene is a housekeeping gene. COS cells transfected with alpha-MIIx cDNA containing the full-length open reading frame showed an increase of alpha-mannosidase activity. The alpha-MIIx gene was mapped to human chromosome 15q25, whereas the alpha-MII gene was mapped to 5q21-22.

Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro.

Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.

[Successful treatment by ranimustine (MCNU) of a patient with B-cell prolymphocytic leukemia (B-PLL)].

A 66-year-old female was admitted to our hospital because of leukocytosis, anemia and splenomegaly in August 1989. The white cell count was 3.49 x 10(10)/l with 88.5% of the leukemic cells which were morphologically similar to prolymphocytes. On flowcytometric analysis, the leukemic cells were found to be positive for B-cell markers such as CD19, CD20, FMC7, Sm-IgM and Sm-IgD and negative for CD5 and CD25. The chromosome analysis demonstrated hyperdiploidy of 48, XX, (+3, +18). She was diagnosed as having B-cell prolymphocytic leukemia, and treated with alpha-interferon and VP therapy with progression. Complete remission was achieved after three courses of ranimustine (MCNU) administration. She relapsed after about one year without therapy, but when MCNU was administered again, a secondary remission followed. The prolymphocytes during the relapse stage also had the phenotypes of CD11b, CD13 and CD25. This case is considered to be rare with respect to both complete remission by MCNU and the immunophenotypic change of leukemic cells during the relapse period.

Enhancing effects of IL-2 on M-CSF production by human peripheral blood monocytes.

Monocytes have the capacity to produce granulopoietic factors such as M-CSF and G-CSF. Our findings here showed that interleukin-2 (IL-2), at a concentration of more than 0.05 ng/ml, led to a 12-fold increase in the production of M-CSF in the human peripheral blood mononuclear cells after 72 h incubation compared to the control culture. Even in purified monocyte cultures with added IL-2, a 3-fold increase in M-CSF production was observed at an IL-2 concentration of 50 ng/ml. The enhancing effect of IL-2 on M-CSF secretion was also observed when IL-2-stimulated non-phagocytic cell-conditioned medium was added to monocyte cultures. These results indicated that IL-2, both directly and indirectly, activated monocytes to enhance the production of M-CSF. In addition, the expression of IL-2 receptor (CD25) on monocytes was more enhanced in cultures containing IL-2 than in cultures without IL-2. On the other hand, IL-2 did not induce G-CSF production in purified monocytes. These in vitro results suggest that when IL-2 is used clinically, the various biological activities of M-CSF should also be taken into consideration.

Angiotropic lymphoma of paranasal sinuses with initial symptoms of oculomotor nerve palsy.

A 78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphoma appears very significant, as this disorder could be well controlled by systemic chemotherapy.

[Within-day and day-to-day variations of serum M-CSF levels in healthy volunteers].

We have investigated on within-day and day-to-day variations of serum M-CSF levels in healthy volunteers (ranges of age: 20-21 years old). M-CSF levels in serum were measured using enzyme-linked immunosorbent assay (ELISA). Serum M-CSF levels in early morning were 1.31 +/- 0.30 ng/ml (mean +/- SD, n = 10) in male volunteers, 1.50 +/- 0.13 ng/ml (n = 10) in female volunteers. No significant difference was observed between male and female volunteers in serum M-CSF levels. No significant within-day variations in serum M-CSF levels were also observed. Serum M-CSF levels in period of thirteen days in each individual person were almost constant (n = 5). The inverse correlation was observed between M-CSF levels and number of neutrophils. The correlation, however, was not observed between M-CSF levels and number of monocytes. The present results suggest that there are mechanisms in vivo which maintain serum M-CSF in a constant level in each individual person.

[Detection of granulocyte-macrophage colony-stimulating factor activity in the supernatant of the cultured leukemic cells of adult T-cell leukemia with eosinophilia].

An adult T-cell leukemia (ATL) accompanied with eosinophilia is described. A 75-year-old female was admitted to our hospital because of lymphadenopathy. Her leukocyte count was 73,300/microliters, with 35.5% abnormal lymphocytes and 19% eosinophils. A majority of lymphocytes expressed CD4+CD8-. Acute ATL was diagnosed, since anti-HTLV-1 antibody in her serum and monoclonal integration of HTLV-1 proviral DNA in her peripheral mononuclear cells were detected. She was treated with THP-adriamycin, cyclophosphamide (CPA), and vincristine (VCR). Abnormal lymphocyte and eosinophil counts decreased and there was improvement in the lymphadenopathy. However she then complained of lymphadenopathy again. Her leukocyte count rose to 76,300/microliters, with 89% abnormal lymphocytes. Combination therapy with CPA, VCR, and doxorubicin was started and there was a temporal regression in lymphadenopathy, but her lymphadenopathy recurred and she died. The activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected in the supernatant of the cultured ATL cells, although interleukin-3, interleukin-5, and GM-CSF activities were not detected in her serum. It seems likely that the secretion of GM-CSF by ATL cells are responsible for the eosinophilia.

[Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders].

Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH-rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP.

Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation.

We investigated the interactions between human erythropoietin (hEpo) and serum factor(s) on murine megakaryocyte (MK) colony formation. Serum-free cultures supported the growth of a large number of murine MK colonies in the presence of murine interleukin-3 (mIL-3). The addition of fetal calf serum (FCS) to mIL-3-containing cultures resulted in only a minimal increase in the number of murine MK colonies. In contrast, hEpo alone had no murine MK colony-stimulating activities in serum-free cultures. hEpo required the presence of FCS, murine serum, or human serum in cultures to promote murine MK colony growth and synergized with these sera to stimulate murine MK colony formation. Furthermore, sera from patients with aplastic anemia showed higher synergistic activities with hEpo than sera from hematologically normal persons (normal human serum). When normal human serum was fractionated by gel-filtration chromatography, two peaks with the synergistic activity were observed in the eluent. However, serum did not show any synergistic effects with hEpo on the growth of murine GM colonies or murine colony-forming unit-erythroid-derived colonies. Although human serum synergized with hEpo to stimulate murine MK colony formation, human cytokines such as IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) failed to induce murine MK colony formation in Epo-containing cultures. In cultures containing human IL-1 alpha + human IL-6 + hEpo as well as in cultures containing hEpo, human IL-3 and human GM-CSF failed to show stimulatory effects on murine MK colony formation. Moreover, the synergistic activity of human serum with hEpo could not be neutralized by antibodies such as antihuman IL-1 alpha, antihuman IL-3, antihuman IL-4, antihuman IL-6, antihuman G-CSF, and antihuman GM-CSF. Our data show that serum contains a growth factor(s) that synergizes with Epo to stimulate the proliferation and differentiation of MK precursors, and strongly suggest that this factor(s) is an unique growth factor(s) that is distinct from IL-1 alpha, IL-3, IL-4, IL-6, G-CSF, and GM-CSF.

[Adult T cell leukemia with cytomegalovirus retinitis].

A 49-year old female in the course of chemotherapy for adult T-cell leukemia (ATL) noticed blurred vision and visual field defect in her right eye on February 26, 1991. Ophthalmoscopic findings showed exudative necrotizing retinitis with white exudative patches and scattered retinal hemorrhages in both eyes. CMV was isolated from the urine by the shell vial cell culture assay. Anti-viral therapy was commenced using ganciclovir and gamma-globulin, which are rich in anti-CMV antibodies. The exudative lesions were absorbed gradually. The ocular signs and symptoms agreed with the patient's systemic immunosuppressed T cell function state. CMV retinitis should be considered in the differential diagnosis of retinitis in immunocompromised patients. CMV retinitis will certainly be found more frequently in accordance with the increasing number of immunocompromised hosts who have received immunosuppressive therapy or transplantation.

[Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) therapy that improved lymphadenopathy in a patient with B cell non-Hodgkin's lymphoma].

A 70-year-old man was admitted to our hospital on March 9, 1989 because of fever, superficial generalized lymphadenopathy, upper abdominal mass and right pleural effusion. The diagnosis of non-Hodgkin's lymphoma (follicular medium sized cell type, B cell) was made by a biopsy of the neck lymph node. Peripheral blood mononuclear cells were obtained from the patient by cytopheresis. The cells were cultured for 8 days with interleukin-2 (IL-2) to generate Lymphokine-activated killer (LAK) cells. The patient received a total of 7.7 x 10(9) LAK cells intravenously over a period of 3 weeks. He also received continuous intravenous infusion of IL-2 for 17 days, starting 2 days before the first infusion of LAK cells. After this therapy, although his superficial generalized lymphadenopathy disappeared or decreased in size, the size of the upper abdominal mass did not decrease. Therefore, it is suggested that adoptive immunotherapy is a beneficial treatments for B cell lymphoma. However, LAK cells should be generated in much larger quantities for a more successful therapeutic result.

[Adult T-cell leukemia with cervical bone tumor showing immunophenotypic change].

A 60-year-old man born in Miyazaki prefecture was admitted to our hospital complaining of skin rash in December 1989. On hematological examinations, leukocyte count was 14,200/microliters with 49% of abnormal lymphocytes showing lobulated nuclei. The surface marker study revealed their phenotype as CD4+8-. Anti human T cell leukemia virus type I (HTLV-I) antibody and monoclonal integration of proviral DNA were positive. From the above results, he was diagnosed as adult T-cell leukemia (ATL). Abnormal lymphocytes gradually decreased without treatment after the first admission. In January, 1990, he began to complain of neck pain. Two months later he was readmitted because of paresis of extremities and disturbance of urination. Vertebral bone mass and a compressed spinal cord in the 4th cervic level were confirmed by MR imaging. He received a resection of tumor and an anterior fusion of vertebrae. The bone tumor was histologically diagnosed as malignant lymphoma, diffuse medium-size cell type and the infiltrating cells had their phenotype as CD4+8+. He was postoperatively treated with combination chemotherapies, but neurological abnormalities did not improve. He died of pneumonia on 35 days after the operation. A postmortem examination revealed extradural tumor formation with ATL cells. This case is considered to be rare in respect of both the disappearance of most peripheral abnormal lymphocytes without any treatments and the cervical bone tumor showing immunophenotypic change.