Cardiac Involvement of Adult T Cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a refractory T-cell lymphoma with variable clinical profiles, commonly exhibiting extra-nodal involvement. The myocardial involvement of ATL is often detected at an autopsy; however, the development of a symptomatic cardiac mass due to ATL is extremely rare. We herein report a 65-year-old man with ATL who developed cardiac symptoms due to a rapidly enlarging left ventricular mass soon after the initiation of systemic chemotherapy. We also summarize previously reported cases of symptomatic ATL with cardiac involvement.

Lactic Acidosis and Hypoglycemia in a Patient with Gastric Diffuse Large B-Cell Lymphoma due to the Warburg Effect.

Lactic acidosis is pathophysiologically classified into type A and type B. The latter is a rare but potentially life-threatening emergency, mainly described in hematological malignancies. The association between Type B lactic acidosis and malignancy is known as the Warburg effect. Patients with the Warburg effect have a very poor prognosis. Herein, we report a case of gastric diffuse large B-cell lymphoma (DLBCL) with severe lactic acidosis and hypoglycemia owing to the Warburg effect that were effectively treated by prompt introduction of chemotherapy. A 73-year-old woman with a 2-month history of abdominal distension was referred to us for suspected peritoneal cancer. Pathological examination revealed gastric DLBCL with peritoneal dissemination. After hospitalization, blood test results revealed prolonged hypoglycemia, with a blood sugar level of 50-70 mg/dL; severe lactic acidosis with pH 7.166; lactate level 12.7 mmol/L; and base excess -21.0 mEq/L, despite continuous administration of glucose and sodium bicarbonate. The cause of lactic acidosis and/or hypoglycemia was considered to be the Warburg effect. We initiated a 50% reduced-dose CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) chemotherapy regimen without rituximab until information on the CD20-positive status was available. During chemotherapy, acidosis, hypoglycemia, and impaired consciousness promptly improved. If lactic acidosis or hypoglycemia is present in patients with malignant tumors, it is important to suspect the possibility of the Warburg effect and to introduce cancer treatment as soon as possible.

Hodgkin's lymphoma preceded by haemophagocytic lymphohistiocytosis.

A 71-year-old woman was admitted because of persistent fever for 2 weeks. A diagnosis of haemophagocytic lymphohistiocytosis (HLH) was made on the basis of persistent high fever, pancytopoenia, hyperferritinaemia, increased soluble interleukin-2 receptor (sIL-2R) levels and histiocytosis and hemophagocytosis in the bone marrow. CT showed neither infection nor lymphadenopathy. After administration of prednisolone, haematological findings improved and the fever resolved; however, the patient developed persistent fever after 6 months. In addition, levels of lactate dehydrogenase and sIL-2R increased again. CT scans revealed diffuse lymphadenopathy, and Hodgkin's lymphoma was diagnosed by lymph node biopsy. Progression of pancytopenia was observed, and bone marrow examination showed a relapse of HLH. After six courses of chemotherapy were given for Hodgkin's lymphoma, complete remission was achieved with no evidence of pancytopenia. Hodgkin's lymphoma may be the underlying cause in HLH cases of unknown aetiology. Hence, the clinical course should be carefully monitored even in the absence of lymphadenopathy.

Masked t(15;17) APL with the insertion of PML-RARalpha fusion gene in 4q21.

Most cases of acute promyelocytic leukemia (APL) are characterized by the reciprocal translocation t(15;17); however, several complex variant translocations have also been reported. Here we report complex cytogenetic abnormalities without t(15;17) assayed by the G-banding method in a 62-year-old woman with the typical morphology and clinical features of APL. Based on spectral karyotyping and FISH analyses, we confirm the insertion of a cryptic chromosomal segment containing the PML/RARalpha fusion gene. The patient achieved complete remission after treatment with all-trans retinoic acid (ATRA) alone. Although the mechanism of this cryptic variant insertion is not known, we conclude that the insertion of PML-RARalpha fusion into 4q21 seems not to alter the effectiveness of treatment with ATRA.

[Case of multiple nodular lesions of bilateral kidneys with IgG4-related systemic disease].

A 59-year-old woman was admitted to our hospital because of a pancreatic mass lesion. Serum gamma-globulin and IgG4 levels were elevated to 2.2 g/dL and 1,310 mg/dL, respectively. Computed tomography examination revealed multiple low-density areas without enhancement by contrast in the pancreatic body and bilateral kidneys. Endoscopic retrograde cholangiopancreatography images demonstrated diffuse narrowing of the main pancreatic duct with an irregular wall from the body to the tail of the pancreas. Positron emission tomography examination revealed intense 18F-fluorodeoxyglucose uptake by the pancreas and kidneys. Accordingly, the patient was diagnosed as having IgG4-related autoimmune pancreatitis. In addition, the findings of a renal tissue specimen obtained by biopsy demonstrated IgG4-positive plasma cell infiltration in both abnormal mass lesions and normal regions by imaging, leading to the final diagnosis of IgG4-related sclerotic disease. The patient was treated with prednisolone (30 mg/day), and the size of the pancreatic and renal lesions markedly decreased four weeks later. We report here a rare case of IgG4-related autoimmune pancreatitis with multiple renal lesions, which were confirmed by renal biopsy.

A new cytogenetic abnormality, t(2;7)(q33;q36), in acute promyelocytic leukemia.

We report the case of a patient with acute promyelocytic leukemia (APL) carrying a novel chromosomal abnormality, t(2;7)(q33;q36). The 54-year-old woman was morphologically diagnosed with APL through bone marrow aspiration. The proportion of blast cells in bone marrow was 78%, including cells displaying Auer rods and faggot cells. Chromosomal analysis revealed the karyotype 46,XX,t(2;7)(q33;q36)[17]/46,XX[3]. The t(15;17) was not detected with conventional cytogenetic analysis. However, reverse transcriptase-polymerase chain reaction revealed the presence of a PML/RARA fusion gene. Cells displaying t(2;7)(q33;q36) disappeared after complete remission was achieved, using induction chemotherapy. Although several additional chromosomal abnormalities have been reported, this t(2;7)(q33;q36) without the classic t(15;17) represents a novel chromosomal abnormality associated with APL.

Nano-scale distribution of ZnO free exciton luminescence in ZnO:Zn microcrystals and its modification under electron beam excitation.

The dependences of cathodoluminescence (CL) from ZnO:Zn phosphor powder upon local space, accelerating voltage and beam current have been investigated at room temperature. Ultraviolet (UV) luminescence, which is hard to be observed in photoluminescence (PL) at room temperature, has been clearly observed in CL as well as green luminescence. The intensity ratio of the UV luminescence to the green one varies from point to point. From the comparison with PL, the UV luminescence is attributed to the recombination of ZnO free excitons. The UV luminescence is little observed at low accelerating voltage where, similar to the excitation light for PL measurement, the electron beam penetrates into only the surface depletion layer where free excitons are unstable due to the surface electric field. However, the UV luminescence from the depletion layer becomes observable at large beam current because of the suppression of the electric field in the depletion layer caused by injected electrons.

A novel c-kit positive biphenotypic acute leukemia cell line, TMBL-1, carrying a p53 point mutation.

We established and characterized a c-kit positive cell line from the bone marrow of a patient with biphenotypic acute leukemia (BAL). The cell line, designated TMBL-1, carried a His-175 mutant p53. The immunophenotype of the primary leukemia cells at diagnosis was cytoplasmic CD3+, CD7+, CD13+, CD33-, interleukin-7 (IL-7) receptor+ and c-kit -. However, leukemia cells in relapse and TMBL-1 cells were CD33+ and c-kit +. Immunophenotypically, TMBL-1 is a BAL cell line that coexpresses T-lymphoid and myeloid markers which fulfill the criteria of the European Group for the Immunological Characterization of Leukemia. Stem cell factor (SCF), a key regulator of hematopoiesis signaling through c-kit, enhanced the proliferation of TMBL-1 cells. Direct sequencing revealed the conversion at codon 175 of the p53 gene in the TMBL-1 cells. Primary leukemia cells in relapse also carried the same point mutation but not at diagnosis. Moreover, TMBL-1 cells are sensitive to paclitaxel, which could induce p53-independent apoptosis. The biphenotypic features and p53 mutation may be associated with progression to a more malignant type. This cell line may provide new information on the role of SCF in the overlapping area between early T-lymphoid/myeloid cells, and help in the design of new therapies targeted towards p53 mutations.

Arsenic trioxide induces apoptosis in HTLV-I infected T-cell lines and fresh adult T-cell leukemia cells through CD95 or tumor necrosis factor alpha receptor independent caspase activation.

Arsenic trioxide (As2O3) has been reported to induce apoptosis in human T-cell leukemia virus type-I (HTLV-I) infected T-cell lines and fresh adult T-cell leukemia (ATL) cells and to induce G1 phase accumulation in HTLV-I infected T-cell lines. The present study aimed to clarify the pathway of As2O3-induced apoptosis in HTLV-I infected T-cell lines, MT-1 and MT-2, and fresh ATL cells separated from peripheral blood of patients with acute or chronic type ATL. Cells were treated up to 72 h at clinically tolerable concentrations of As2O3 (1-2 micromol/l) shown to be safe in patients with acute promyelocytic leukemia (APL). Activation of caspases 3, 8, and 9, loss of mitochondrial transmembrane potential and cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP) were observed during As2O3 treatment. Furthermore, prior exposure to a broad-spectrum caspase inhibitor blocked As2O3-induced apoptosis but not G1 phase accumulation. While pre-treatment with a CD95 receptor-blocking antibody (Ab) or a TNF-alpha neutralizing Ab did not show such inhibitions in these cells. In conclusion, As2O3 induces apoptosis in HTLV-I infected T-cell lines and fresh ATL cells through CD95 or TNF-alpha receptor independent caspase activation.

Augmentation of the activity of an immunotoxin, anti-Tac(Fv)-PE40KDEL, in T cell lines infected with human T cell leukemia virus type-I.

Therapy with an immunotoxin, anti-Tac(Fv)-PE38, which is a conjugate of the variable domains of an anti-Tac monoclonal antibody and Pseudomonas exotoxin, was reported to be useful for adult T cell leukemia (ATL) patients but a considerable amount of the immunotoxin is needed for the therapy and some side effects were also observed. We have previously demonstrated that an immunotoxin, anti-Tac(Fv)-PE40KDEL, showed strong cytotoxic effects on malignant cells from ATL patients. Therefore, we searched for agents that enhance the effects of the immunotoxin. PAK-200, FK-506, quinidine, cepharanthine and cyclosporine A (CsA) augmented the ability of the immunotoxin to inhibit protein synthesis in two human T cell leukemia virus type-I infected T cell lines, KUT-1 and KUT-2. CsA was the most potent agent in both the cell lines. Augmentation of the cytotoxic effect of the immunotoxin by these agents, especially CsA, may be useful in the immunotoxin therapy of ATL.