Low frequency of BCL10 gene mutations in B-cell non-Hodgkin's lymphoma.

The BCL10 gene was identified at the breakpoint region of the t(1;14)(p22;q32) translocation in mucosa-associated lymphoid tissue lymphoma. Initially, mutations in the BCL10 gene were reported to occur at a high frequency in various types of lymphomas and solid tumors. However, subsequent studies showed that the mutations were rarely recognized. To evaluate the frequency and spectrum of its mutations in B-cell non-Hodgkin's lymphoma (B-NHL), we screened 56 cases with B-NHL by mutation analysis of exons 2 and 3 of the gene. In addition to 2 polymorphisms, a frame-shift mutation and a missense mutation were identified in 2 cases (3.6%): 1 with diffuse large B-cell lymphoma and the other with mantle cell lymphoma. Both cases showed mutations within exon 3, resulting in a C-terminal truncation in the former and a C-terminal amino acid substitution in the latter. Reverse transcriptase-polymerase chain reaction analysis of the former case revealed that both the mutated and the wild-type alleles were transcribed with or without a sequence modification. Our results, together with recent reports, indicate that BCL10 gene mutations take place in a small population of B-NHL and are not associated with specific histological subtypes.

[Primary renal non-Hodgkin's lymphoma presenting as immune thrombocytopenia].

A 25-year-old man was admitted to our hospital because of hematuria, anemia and thrombocytopenia. Laboratory examinations revealed an increased number of bone marrow megakaryocytes and an increased level of platelet-associated immunoglobulin G, suggesting immune thrombocytopenia. Computed tomography of the abdomen showed enlargement of the bilateral kidneys with multiple low-density areas, although neither lymphadenopathy nor hepatosplenomegaly was evident. After amelioration of the thrombocytopenia by prednisolone therapy, open renal biopsy was performed and a diagnosis of diffuse large B-cell non-Hodgkin's lymphoma was made. The patient achieved complete remission after CHOP therapy. This was thought to be a rare case of primary renal non-Hodgkin's lymphoma initially presenting as immune thrombocytopenia, which was treated successfully by chemotherapy.

[CD19-positive acute myeloblastic leukemia developed 12 years after the onset of hypereosinophilic syndrome].

We report a rare case of hypereosinophilic syndrome (HES) that developed to acute myeloblastic leukemia (AML). The patient, a 34-year-old man, presented with eosinophilia of unknown origin (white blood cells 38,200/microliter with 74% eosinophils) and pericardial effusion, and was diagnosed as having HES with a normal karyotype. He received four cycles of combination chemotherapy including cyclophosphamide, cytosine arabinoside and vindesine, and thereafter remained in remission. After 12 years, he was referred to our hospital because of fever and malaise. On admission, CBC showed white blood cells 3,000/microliter with 70% myeloblasts and 3% eosinophils. The bone marrow was hypercellular with 95% blasts, which were negative for myeloperoxidase (MPO) staining. Immunophenotype analysis revealed that the cells were positive for CD13, CD19, CD34, HLA-DR and cytoplasmic MPO. CD19-positive AML was diagnosed. Cytogenetic analysis showed 46, XY, t(6;21)(q13;q22), add(7)(q11) in 19 of 20 metaphase spreads. Rearrangement of the AML1 gene at 21q22 and fusion of the BCR/ABL gene could not be detected by fluorescence in situ hybridization analysis. The patient received combination chemotherapy and achieved a complete remission. Chromosome aberrations involving 7q as well as 21q22 suggested that the initial chemotherapy for HES might have been implicated in the pathogenesis of acute leukemia in this case.

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation.

We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.