Peptides derived from the whole sequence of BCR-ABL bind to several class I molecules allowing specific induction of human cytotoxic T lymphocytes

Chronic myeloid leukemia (CML) is characterized cytogenetically by a t(9;22) translocation which generates a hybrid bcr-abl gene, encoding a p210^bcr-abl fusion protein. The induction in vitro of leukemia-specific T cells reactive with p210^bcr-abl is a strategy developed for an immunological therapeutic approach in CML. Peptides from the junction region of this chimeric protein have been considered as potential targets for a cytotoxic response against leukemic cells. However, only a few peptides encompassing the two p210^bcr-abl breakpoints have been shown to bind to the most common HLA class I molecules, which limits the number of patients who could benefit from this approach. We assume that the presence of chimeric BCR-ABL protein in leukemic cells may affect processing and delivery of peptides, possibly giving rise to new epitopes at the cell surface. We selected 162 peptides from the whole sequence of this protein, including 14 peptides of the b2a2 and b3a2 junctions, which had an anchor motif for a common HLA class I molecule. We tested their ability to bind to eight HLA class I molecules (HLA-A1, -A2, -A3, -A11, -B7, -B8, -B27, -B44). We identified 48 peptides from outside the junction region, with intermediate or strong binding capacities to these HLA class I molecules contrasting with only six junction peptides with a moderate binding capacity to HLA-A3/A11, -B8, or -B44 molecules. Moreover, cytotoxic T lymphocyte lines specific for various peptides outside the junction were generated from peripheral blood mononuclear cells of HLA-A2 or -B7 healthy donors and from one CML patient. These results contribute to evaluation of immunity to the BCR-ABL chimeric protein. Further studies are required to investigate whether such epitopes are correctly processed and presented by leukemic cells.     

Malignant tumor of humerus with features of "adamantinoma" and Ewing's sarcoma

This female patient was born in 1935 and died in 1976 with a malignant bone tumor involving the proximal humerus following multiple local recurrences, axillary lymph node metastases, and pulmonary metastases. Histologically, over the course of time, there was an increase in features of an atypical Ewing's sarcoma, at the expense of findings of a typical, extra-cranial so-called adamantinoma. In contrast to another report, our case showed neither epithelial nor endothelial features on fine structural examination, but rather primitive mesenchymal cells, as is described for Ewing's sarcomas.     

肢端黏液样炎性纤维母细胞肉瘤2例及文献复习

目的探讨肢端黏液样炎性纤维母细胞肉瘤的临床病理学特征及鉴别诊断。方法对2例发生在下肢末端的黏液样炎性纤维母细胞肉瘤进行光镜观察和免疫组化标记，并复习文献。结果2例发生在下肢末端的病程较长的渐进性肿块，术后局部复发。镜检：病变呈多结节状，边界不清；黏液样基质中见数量不等的各类炎细胞浸润，散在或灶性分布梭形、奇异形和多空泡状脂肪母细胞样3种形态的瘤细胞。免疫表型：肿瘤细胞Vim弥漫阳性，CD68和CD34灶性阳性，CK、SMA、HHF-35、S-100蛋白、CD45、CD45R0、CD15、CD30均阴性。结论此病病程较长，术后易局部复发，是一种低度恶性的肿瘤。鉴于病变黏液样基质及各类炎细胞浸润的背景较为突出，而特征性的瘤细胞稀疏，应注意与炎症性病变或具有相似组织形态的良性或恶性肿瘤鉴别。     

Identification of CD56 and CD57 by flow cytometry in Ewing’s sarcoma or primitive neuroectodermal tumor

 CD56 and CD57 are commonly considered as natural killer and neuroectodermal markers, but their expression has been identified in a wide spectrum of neoplasms including some cases of Ewing’s sarcoma (ES) and primitive neuroectodermal tumor (PNET). We report two cases of small, round blue cell tumor (SRBCT), in which flow cytometry immunophenotyping (FCI) detected strong expression of CD56 and CD57 (one case). Immunohistochemical staining with Leu-19 and Leu-7 confirmed the FI results. Although CD56 and CD57 expression is consistent with ES/PNET, it can be potentially misleading if results of FCI are interpreted in the absence of other findings. These cases suggest the utility of FCI in undifferentiated SRBCT. The literature on CD56 and CD57 expression in ES/PNET is reviewed and discussed. Received: 5 January 1998 / Accepted: 19 February 1998     

Kaposi’s sarcoma: is the hunt for the culprit over now?

 Patients suffering from the acquired immune deficiency syndrome (AIDS) have a 20000-fold increased risk of developing a severe form of Kaposi’s sarcoma (KS), a previously rare malignancy involving sharply defined nodular lesions of the skin and/or oral mucosa. Epidemiological evidence has long suggested that an infectious agent is the probable cause of KS. Recently sequences from a putative new herpesvirus have been found to be associated with KS in virtually 100% of the cases analyzed. The suspected etiological agent, a new human herpesvirus termed Kaposi’s sarcoma associated herpes virus (human herpes virus 8) has now been propagated in cell culture. This significant advance should form the basis for a detailed analysis of the pathogenetic mechanisms involved in the development of KS. Received: 4 June 1996 / Accepted: 5 August 1996     

Epithelioid sarcoma in children and adolescents

Summary Six cases of epithelioid sarcoma were studied by conventional light microscopy and immunohistochemistry. The six cases account for 1.4% of the 417 cases of soft tissue sarcoma collected at the Paediatric Tumor Registry, Kiel. The average age of the five male and one female patient was 10.8 years (median: 13 years). Particular clinical findings included the location of the tumours; three were found in the pelvis, two in the head and neck, and one in the hand. Four patients are living without disease, and one patient died of disease three years after diagnosis.Histologically, four of the six tumours revealed multinucleated giant cells. Immunohistochemically using a panel of mono- and polyclonal antibodies all cases stained positively for vimentin, cytokeratin, epithelial membrane antigen (EMA), and human milk fat globulin (HMFG-2). Five cases were positive for neuron specific enolase (NSE), and three stained positively for protein S-100. A positive reaction for alpha-1-antichymotrypsin was noted in two cases. These immunohistochemical findings attest to the multidirectional differentiating capabilities of epithelioid sarcoma and support the concept of derivation from a multipotent mesenchymal stem cell.This study was supported in part by a grant from the Bundesminister für Arbeit und Sozialordnung and the Deutsche Forschungsgemeinschaft (Schm 613/1-1)     

Treatment of atypical leishmaniasis with interferon γ resulting in progression of Kaposi's sarcoma in an AIDS patient

Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being reported in increasing frequency. A 40-year-old German bisexual patient with full-blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain, diarrhea, and weight loss but without fever.Leishmania amastigotes were initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's sarcoma lesion but were later also recovered from bone marrow and lymph node. The patient received three courses of a combination of pentavalent antimony and interferon-. In addition to the common side effects such as fever, thrombocytopenia, and elevated amylase and lipase, a vivid progression of the Kaposi's sarcoma was noted. Tumor progression was temporally closely associated with treatment with interferon-. Because this phenomemon has also been observed in other patients, we advise caution when using interferon- in patients with Kaposi's sarcoma.Abbreviations AIDS acquired immunodeficiency syndrome - HIV human immunodeficiency virus - KS Kaposi's sarcoma Correspondence to: H. Albrecht     

Synovial sarcoma: an immunohistochemical study

The immunohistochemical staining pattern of 18 cases of synovial sarcoma with two epithelial-specific monoclonal antibodies is described. This is compared with normal synovium, cases of giant cell tumour of tendon sheath (benign synovioma) and a variety of spindle celled sarcomas. Sixteen cases of synovial sarcoma showed staining of the epithelial component with at least one antibody. No staining was seen in normal synovium or in giant cell tumours of tendon sheath. A small number of malignant schwannomas contained groups of cells which stained positively whilst other spindle cell sarcomas either did not stain or showed 'cross-reaction' type staining only. These results add weight to the proposition that synovial sarcomas do not arise from normal synovium, despite their morphological similarities, but from mesenchymal connective tissue. It is also shown that immunohistochemical staining with anti-epithelial antibodies will emphasize the biphasic pattern of synovial sarcomas allowing their distinction from other sarcomas.     

Production of a strain of human osteogenic sarcoma cell line HOS transplantable into nude mice and rats

All-Union Oncologic Scientific Center, Academy of Medical Sciences of the USSR. Institute of Virology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 10, pp. 471–472, October, 1988.     

A hybrid form of myeloid/NK-cell acute leukemia and myeloid/NK-cell precursor acute leukemia

Natural killer (NK)-cell leukemia/lymphoma is a rare entity that has been defined only in recent years. In the Revised European-American Lymphoma and World Health Organization classifications, only the mature NK-cell malignancies are included. However, at least 3 types of precursor NK-cell neoplasms have been reported in the literature. These include myeloid/NK-cell acute leukemia, myeloid/NK-cell precursor acute leukemia, and blastic NK-cell lymphoma/leukemia. These leukemias are characterized by the presence of blasts, which express CD56, in the peripheral blood, bone marrow, lymph nodes, and/or extranodal tissues. We report a case that is morphologically consistent with myeloid/NK-cell acute leukemia but immunologically is myeloid/NK-cell precursor acute leukemia. This case is unique in its cutaneous presentation without involvement of the peripheral blood. Extensive flow cytometric studies were performed on the skin biopsy and bone marrow aspirate specimens, which included many markers that had not been tested before in these entities. The clinical implications of these findings are discussed.