Hiroshi Narumi

Non-Hodgkin's lymphoma developing in a pacemaker pocket

A 29-year-old man developed diffuse large B-cell lymphoma in a subpectoral pacemaker pocket that 6 years previously had been created in the chest for a titanium-covered pulse generator. The patient had an 8-cm—diameter dark red tumor with necrotic tissue on a keloidal surgical scar in the left side of the chest. Left axillary lymphadenopathy also was present. Laboratory studies showed an increased level of soluble interleukin 2 receptor and a normal level of lactose dehydrogenase. A biopsy specimen showed a diffuse large B-cell phenotype and monoclonal immunoglobulin H gene rearrangement. A gallium scintigraphy study showed abnormal accumulation in the left chest and left axilla. On the basis of these findings, we diagnosed diffuse large B-cell lymphoma, stage II. The patient received THP-COP chemotherapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone) and radiotherapy, achieved complete remission, and was free of disease for 16 months after treatment. This case suggests that there was a relationship between the development of non-Hodgkin’s lymphoma and the presence of chronic inflammation in the pulse generator pocket.

Familial occurrence of chronic neutrophilic leukaemia

A father and son who both developed chronic neutrophilic leukaemia (CNL) are reported. The father, aged 63, had been exposed to radioactive fallout after the atomic bomb attack on Hiroshima; he presented with hepatosplenomegaly and neutrophilic leucocytosis, and died of intracerebral haemorrhage 1 month after diagnosis. 4 years later his son, then aged 44, presented with neutrophilic leucocytosis. Leukaemic transformation to acute myelogenous leukaemia (AML‐M1) occurred, and he died of refractory leukaemia 4 months after the diagnosis of CNL. This is the first report of this rare disease occurring in family members; genetic effect due to radioactive poisoning was suspected in the development of CNL in these two cases.

Identification of an epitope derived from CML66, a novel tumor‐associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen‐A*2402‐restricted cytotoxic T lymphocytes

CML66 is a newly identified differentiation antigen that is expressed broadly in human leukemia and solid tumors, but its physiological function remains unknown. In the present study, to clarify the feasibility of CML66‐targeted cancer immunotherapy, we attempted to identify cytotoxic T lymphocyte (CTL) epitopes derived from CML66. An immunogenic CML66‐derived epitope (amino acid residues 76–84; YYIDTLGRI) capable of inducing human leukocyte antigen (HLA)‐A*2402‐restricted CTL specific for this peptide was identified. CML66‐derived peptide‐specific CTL efficiently lysed human leukemia cells, but not normal cells, in a HLA‐A*2402‐restricted fashion. Quantitative real‐time polymerase chain reaction revealed that CML66 mRNA is expressed abundantly in primary acute myeloid leukemia cells, acute lymphoid leukemia cells, and chronic myelogenous leukemia cells in advanced phase, and that the expression level of CML66 mRNA in normal cells is low compared with that in leukemia cells. CML66‐specific CTL precursors were detected in the peripheral blood of patients with acute leukemia. These data indicate that the CML66‐derived epitope identified in the present study is a new target antigen for cellular immunotherapy of human leukemia. (Cancer Sci 2008; 99: 1414–1419)

Hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17)

We describe a case of hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17). The large leukemia cells had a bizarre nuclear configuration and multiple Auer rods. A bone marrow biopsy specimen revealed a markedly hypocellular marrow (<10% cellularity) in the absence of myelofibrosis. Myelodysplastic features were not detected. Chromosome analysis of marrow cells revealed a karyotype of 92,XXYY,del(2)(q?),t(15;17)(q22;q21)x2. Interphase fluorescence in situ hybridization revealed that the marrow cells were composed of a tetraploid clone carrying double t(15;17) and normal diploid cells. The leukemia responded well to all-trans retinoic acid. We think that the tetraploidy could be caused by endoreduplication or endomitosis of the diploid clone with single t(15;17). The unique karyotype largely contributed to the cell morphology and marrow hypoplasia, while it may not have affected on the prognosis of the acute promyelocytic leukemia.

Sensitivity to Interferon-Alpha and Interferon-Stimulated Gene Factor 3 Binding Activity in Human Chronic Myelogenous Leukemia Cell Line KT-1

The mechanism of responsiveness of chronic myelogenous leukemia (CML) cells to interferon (IFN)-α was examined by using two subclones of CML cell line KT-1 which exhibited significantly different sensitivities to the antiproliferative and apoptosis-inducing effects of IFN-α. IFN-stimulated gene factor 3 (ISGF3) formation by IFN-α was reduced in the IFN-α-resistant subclone compared to the IFN-α-sensitive subclone. We conclude that the level of ISGF3 formation is responsible for the difference in IFN-α responses between these subclones.

Deleted HTLV provirus in peripheral blood cells of a patient with T-cell prolymphocytic leukaemia

We describe the first case of T‐cell prolymphocytic leukaemia (T‐PLL) in which the peripheral blood cells contained a human T‐lymphotropic virus (HTLV) related tax sequence. Serum screening tests for anti‐HTLV‐I/II antibodies were negative. Polymerase chain reaction disclosed the presence of an HTLV‐I tax sequence in the peripheral blood. Other sets of oligonucleotide primers for HTLV‐I gag, pol, env and the long terminal repeat regions and for the HTLV‐II pol region were negative in the DNA of the cells. Although patients with T‐PLL have been reported to be seronegative for HTLV‐I, our findings point to the possibility that HTLV‐I infection might be involved in the aetiology of at least some cases of T‐PLL and that there may be alternative mechanisms involved in HTLV‐associated leukaemogenesis.

Derivative (1;18)(q10;q10) in essential thrombocythemia

This study reports the association of the chromosomal abnormality derivative (1;18)(q10;q10) with essential thrombocythemia (ET) occurring in a 75-year-old woman. Allele-specific polymerase chain reaction also revealed a V617F mutation in the Janus Kinase 2 gene (JAK2) in the platelet compartment in this patient. The der(1;18)(q10;q10) abnormality has previously been reported in two cases of myeloid disorders. The etiological implications for ET of this combination of chromosomal abnormality and JAK2 mutation still remain elusive. This is a novel report of derivative (1;18)(q10;q10) abnormality in ET.

Identification of a novel epitope derived from CML66 that is recognized by anti‐leukaemia cytotoxic T lymphocytes

Down syndrome. British Journal of Haematology, 142, 934–945. Lundin, C., Heldrup, J., Ahlgren, T., Olofsson, T. & Johansson, B. (2009) B-cell precursor t(8;14)(q11;q32)-positive acute lymphoblastic leukemia in children is strongly associated with Down syndrome or with a concomitant Philadelphia chromosome. European Journal of Haematology, 82, 46–53. Mitelman, F., Johansson, B. & Mertens, F. (2009) Mitelman database of chromosome aberrations in cancer. Available at: http://cgap.nci. nih.gov/Chromosomes/Mitelman. Schaad, K., Strömbeck, B., Mandahl, N., Andersen, M.K., Heim, S., Mertens, F. & Johansson, B. (2006) FISH mapping of i(7q) in acute leukemias and myxoid liposarcoma reveals clustered breakpoints in 7p11.2: implications for formation and pathogenetic outcome of the idic(7)(p11.2). Cytogenetic and Genome Research, 114, 126– 130.

An unusual, CD4 and CD8 dual-positive, CD25 negative, tumor cell phenotype in a patient with adult T-cell leukemia/lymphoma

Nicholas Casey , Hiroshi Fujiwara, Taichi Azuma, Yuichi Murakami, Makoto Yoshimitsu, Izumi Masamoto, Yuichiro Nawa, Jun Yamanouchi, Hiroshi Narumi, Yoshihiro Yakushijin, Takaaki Hato and Masaki Yasukawa Department of Hematology, Clinical Immunology, and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Japan; Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan; Clinical Laboratory, Kagoshima University Hospital, Kagoshima, Japan; Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan; Cancer Center of Ehime University Hospital, Ehime University Graduate School of Medicine, Toon, Japan; Department of Blood Transfusion and Cell Therapy, Ehime University Graduate School of Medicine, Toon, Japan