Stratification of patients with multiple myeloma (MM) may be important. We investigated 138 MM patients, focusing on correlations between CD20 expression, 11 ; 14 translocation, morphology of MM cells, cyclin D1 immunostaining, and the prognosis. About 15% of patients (7/47cases) were CD20-positive, small mature MM cells, with positive cyclin D1 in the nucleus and 11; 14 translocation. Two color analysis of CD38 x CD20 antigens may be necessary to investigate CD20 expression on MM cells. Rituximab may be effective for the treatment of CD20-positive MM.

A 50-year-old woman developed a subcutaneous tumor in the left lower leg. A biopsy led to the diagnosis of lymphoid malignancy. The malignant cells showed a B-cell immunophenotype. Karyotyping of the cells revealed t(14;18) and t(2;3). The patient was treated with chemotherapy, resulting in a transient response. Subsequently, tumor regrowth and bone marrow recurrence developed. Karyotyping of the bone marrow at relapse revealed a t(8;22) in addition to t(14;18) and t(2;3), which led to a diagnosis of acute lymphoblastic leukemia (ALL)-L3 (FAB). Although the patient was treated with several chemotherapy regimens, the disease was refractory to all the treatments. Fluorescence in situ hybridization (FISH) and the nested polymerase chain reaction (PCR) technique demonstrated rearrangements of the c-myc, bcl-2, and bcl-6 genes. ALL-L3 associated with t(14;18) is known to be complicated frequently with cerebrospinal infiltration and extramedullary lesions, and has a poor prognosis. In our case, the presence of the additional t(2;3) may have enhanced this patient's refractoriness to the treatment.

A 4-year-old boy with Down syndrome (DS) was diagnosed as having acute monoblastic leukemia (AML-M5a). Leukemic cells were CD33+, CD56+ and CD4+, with t(9;11) on cytogenetic analysis and MLL gene rearrangement. After 2 courses of induction therapy using an AML 99-Down protocol failed to obtain complete remission, the patient received cord blood transplantation from an HLA-matched donor (CBT) following a conditioning regimen comprising total body irradiation and cyclophosphamide. Only cyclosporin A was used for graft-versus-host disease prophylaxis. Stem cell transplantation may not be indicated for AML patient with DS in first remission, who display a high rate of life-threatening and fatal toxicity on therapy. This patient remained well controlled in complete remission for 4 years, representing a rare case of DS with chemotherapy-resistant AML successfully treated with a CBT.

We tested the methylation status of tazarotine induced gene 1 (TI(G1) in head and neck cancer cell lines and primary tumors by the methylation-specific polymerase chain reaction (MSP). MSP showed that the TIG1 promoter was methylated in all cell lines. We then used MSP to check the methylation status of TIG1 in primary head and neck cancer (n = 50). MSP showed TIG1 methylation in 31 (62%) head and neck cancers and no methylation in any normal samples. To confirm MSP results, we directly sequenced dense CpG regions. We found that promoter regions contained methylated cytosines. We thus observed a cancer-specific pattern of TIG1 methylation in primary head and neck cancer. Our results support the notion that promoter methylation is an important mechanism of TIG1 gene inactivation and occurs frequently in head and neck cancer. TIG1 methylation represents a new molecular marker for targeting diagnostic and therapeutic approaches in these cancers.

The translocation (15;17) is a typical marker of acute promyelocytic leukemia, whereas t(9;22) is predominantly associated with chronic myelogenous leukemia, and seldom with acute myelogenous leukemia. Furthermore, the association between t(15;17) and t(9;22) in the same cell is extremely rare. We present a case of therapy-related acute promyelocytic leukemia (t-APL) with a subclone accompanied by karyotype 46, XX, t(9; 22)(q34;q11), t(15 ;17)(q22;11 to approximately 12) at onset. A 75-year-old woman was diagnosed as having non-Hodgkin lymphoma of the thyroid gland in July 1997. She was treated with a CHOP-like regimen, but complete remission (CR) was not achieved. She then underwent surgical resection of her thyroid gland, and was treated with etoposide (total dose 16775 mg) from February 1998 to May 2000. In June 2000, having developed t-APL, she was referred to our department. The patient attained CR following treatment with chemotherapy containing all-trans retinoic acid. Ten months later she relapsed, but lost the t(9;22), while maintaining the t(15;17).

Polycythemia vera (PV) is a hematopoietic stem cell clonal disorder, 5 to approximately 10% of which will evolve into acute leukemia. The pathophysiology of leukemic transformation and the best therapy for the leukemic phase of PV is still unknown. A 73-year-old woman was given a diagnosis of PV 17 years previously. However, laboratory data revealed myeloblasts in the peripheral blood with macrocytic anemia and thrombocytosis in March 2003. Bone marrow examination in October 2003 revealed 32.8% myeloblasts with trilineage dysplasia. Chromosomal analysis of the bone marrow cells revealed that 18/22 of mitotic cells had del(20q) and 3/22 of had t(2; 12). The leukemic phase of PV was diagnosed. She achieved not only a hematologic remission, but also cytogenetic remission after interferon (IFN)-alpha treatment. As far as we know, this is the first report of the introduction of IFN-alpha in the treatement of the leukemic phase of PV. Further monitoring of this patient will provide valuable information concerning the pathophysiology of leukemic transformation and the development of effective therapy for the leukemic phase of PV.

A 49-year-old Japanese woman was diagnosed on March 1996 as having thyroid cancer with lung metastasis. Following a total thyroidectomy, she was treated with a total dose of 350 mCi iodine-131 (131I) for metastatic thyroid cancer. Four years later she returned to our hospital under the chief complaint of subcutaneous bleeding. Hematological examinations revealed marked leukocytosis associated with anemia and thrombocytopenia. A bone marrow aspiration showed a hypercellular marrow consisting of 90% blasts negatively stained by myeloperoxidase. Immunophenotyping of the blasts indicated they were CD19, 34, HLA-DR positive but CD3, 10, 13 negative. She was given the diagnosis of pro-B acute lymphoblastic leukemia (pro-B ALL). Cytogenetic analysis showed a chromosomal aberration t(4; 11)(q21; q23) and MLL-AF4 chimeric gene mRNA was detected by RT-PCR analysis. She had never been exposed to any kind of chemoradiotherapy other than 131I therapy and her leukemia showed a t(4; 11) chromosomal aberration and no expression of CD10 on the blasts, which are the characteristics frequently found in therapy-related pro-B ALL patients, suggesting a relationship between the development of pro-B ALL with t(4; 11) and 131I therapy. Although leukemia has been recognized as a late uncommon complication after 131I therapy for thyroid cancer, to the best of our knowledge this is the first patient who developed ALL with t(4 ;11) after 131I therapy among patients with thyroid cancer.

The translocation t(1 ; 14)(p22 ; q32) has been reported only in cases of mucosa-associated lymphoid tissue (MALT) lymphomas. Moreover, bcl-10 is a novel apoptotic signaling gene located at 1p22 and t(1 ; 14)(p22 ; q32) may directly expose bcl-10 to Ig somatic hypermutation. A recent report indicates a pathogenic role of bcl-10 mutation in the progression of MALT lymphomas. In this report, we describe the first case of multiple extranodal diffuse large B-cell lymphoma (DLBCL) with t(1 ; 14)(p22 ; q32). A 70-year-old woman was diagnosed as having DLBCL of multiple extranodal sites (lung, duodenum, colon and kidney). Cytogenetic analysis of a renal lesion revealed the chromosome translocations t(1 ; 14)(p22 ; q32) and both IgH and bcl-10 gene rearrangements were confirmed by Southern blot hybridization. The patient received a regimen of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). She achieved complete remission after six cycles of chemotherapy and has been free of disease for more than five years. This is the first case of bcl-10 gene rearrangement in DLBCL with t(1 ; 14)(p22 ; q32) and this gene may be involved in the pathogenesis of aggressive lymphomas such as MALT lymphomas or in the progression of MALT lymphomas.

We report a rare case of follicular lymphoma which rapidly showed transformation to the Burkitt type of lymphoma after a treatment consisting of chemotherapy and irradiation. A 51-year-old male visited our hospital in August 2000 because of bilateral neck lymphadenopathy. He was diagnosed as having follicular lymphoma (grade 2) (clinical stage IIIA) with complex karyotypic abnormalities involving t(14 ; 18)(q32 ; q21) and CD20 expression. Initially he was followed as an outpatient without chemotherapy. Six months later, he was admitted because of hydronephrosis due to an intrapelvic tumor. He underwent chemotherapy with 4 courses of CHOP regimen following irradiation therapy and a partial response was obtained. Four months after initiation of the treatment, his disease recurred with numb chin syndrome. Bone marrow aspiration revealed bone marrow involvement by lymphoma cells which had a Burkitt-like appearance. A cytogenetic study using bone marrow blood showed complex abnormalities involving t(8 ; 22)(q24 ; q11) in addition to t(14 ; 18). In spite of salvage chemotherapy, the patient died in September 2001.

A 33-years-old man was diagnosed as having undifferentiated carcinoma presenting with right neck lymphadenopathy in December 2000. He obtained complete remission (CR) following chemotherapy, radiation and lymphadenectomy on the right neck. He had multiple para-aorta lymphadenopathy and splenomegaly in December 2001. An open-abdominal lymph node biopsy was performed from which a diagnosis of anaplastic large cell lymphoma was made. CR was achieved with biweekly CHOP, however, the patient suffered from a relapse twice. He underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sister while in non-CR in November 2002. Engraftment was achieved on day 14, and at the same time, complete chimerism was confirmed. Acute grade III graft-versus-host disease (GVHD) developed and was controlled with cyclosporine A and prednisolone. Extensive chronic GVHD was subsequently observed and required systemic immunosuppression. His condition returned to CR after the PBSCT and he sustained complete chimerism. He suddenly died of fulminant thrombotic microangiopathy seven months after the PBSCT. The tumor cells were ALK-positive, CD30-negative and JH rearrangement was detected, and were therefore classified as diffuse large B-cell lymphoma with expression of ALK according to the WHO classification, though they differed from this subtype in some points. Although this case was refractory for chemotherapy with a complex karyotype, the graft-versus-lymphoma effect might have contributed to the sustained CR following the PBSCT.