Cytogenetic studies on patients with chronic T cell leukemia/lymphoma

Cytogenetic studies were performed on three patients with chronic T cell leukemia and on one patient with T cell lymphoma. One of the patients had leukemic cells derived from a suppressor T cell clone, another expressed OKT3, 4, and 8, and cells of the other two were derived from a helper T cell clone. All patients had an abnormal karyotype in peripheral blood or bone marrow cultured with or without mitogen. Modal chromosome numbers were 42 and 44/45 in one patient each and 47 in the 2 others. The structural and numerical abnormalities involved almost all chromosomes, except no. 19 and the X chromosome. All patients had a rearrangement of the long arm of no. 14, with a break at band 14q11;3 patients also had a break at 14q32. An inversion of 14q occurred in two patients; a tandem translocation involving both no. 14 chromosomes and a translocation between no. 14 and no. 17 each occurred in one patient. The break in 14q at band q11 in our cases resembles the chromosome change reported in ataxia telangiectasia. This provides added support for the proposal that a 14q rearrangement involving band q11-12, with or without an accompanying break in 14q32, may confer a proliferative advantage on lymphocytes, especially on those of T cell origin.     

中国人成人T细胞白血病/淋巴瘤12例临床分析

目的 探讨中国人成人Ｔ细胞白血病／淋巴瘤（ＡＬＴＴ）临床特征、鉴别诊断和与嗜人Ｔ细胞病毒Ｉ型（ＨＴＬＶ－Ｉ）感染的关系。方法 外周血淋巴细胞形态学检查用离心涂片法,淋巴细胞免疫分型用间接免疫荧光法,ＨＴＬＶ－Ｉ前病毒ＤＮＡ检测用聚合酶链反应（ＰＣＲ）法并经Ｓｏｕｔｈｅｒｎ Ｂｌｏｔ证实。结果 １２例病人临床表现依次为发热１０例、淋巴结肿大８例、皮肤损害７例、脾、肝大７例、黄疸３例,个别有胸水和肺侵     

Analysis of transformation with epstein-barr virus and phenotypic characteristics of lymphoblastoid cell lines established from patients with hairy cell leukemia

In order to assess the role of Epstein-Barr virus (EBV) in patients with hairy cell leukemia (HCL), we have sought to characterize 1) the ability of EBV to infect and transform hairy leukemic cells in vitro and 2) the phenotypes of cell lines putatively derived from those leukemic cells. Analysis of EBV-induced transformation and the kinetics of Epstein-Barr nuclear antigen (EBNA) induction in leukemic preparations indicated that most leukemic cells were not susceptible to EBV infection but that at least a small subpopulation of leukemic cells could be infected with EBV. Lymphoblastoid cells lines were established after exposure of peripheral blood or splenic cells from HCL patients to B95-8 or QIMR-WIL EBV. Splenic leukemic cell preparations were more sensitive targets for EBV transformation than were peripheral blood cell samples. The newly established cell lines, but not long-established B lines such as Raji, demonstrated high levels of synthesis of p35, (a protein complex expressed abundnatly by cells of a subset of HCL patients) and high levels of tartrate-resistant acid phosphatase (an enzyme relatively diagnostic for HCL). Lymphoblastiod lines from one patient with HCL expressed lambda light chains and no kappa chains as did the patient's leukemic cells. Virus expression in these lines showed that HCL-derived lines had spontaneous earley antigen (EA) and viral capsid antigen (VCA) expression Tranforming EBV could be rescued from HCL-derived cell lines but not from cord blood-derived lines.     

Functional properties of neoplastic T cells in adult T cell lymphoma/leukemia patients from the Caribbean

The neoplastic T cells from five patients with adult T cell lymphoma/leukemia (ATLL), born in the Caribbean, were studied with respect to immunoregulatory activity on pokeweed mitogen (PWM) driven immunoglobulin (Ig) synthesis as well as surface-marker phenotypes with monoclonal antibodies. The neoplastic T cells in all patients had an OKT1+4+8-11+M1-I1-3A1- phenotype, but differed in the reactivity with OKT3. None of the patients' cells exerted helper activity on PWM- induced Ig synthesis. The neoplastic cells of three patients had suppressor activity on PWM-induced Ig synthesis. All patients were positive for human T cell leukemia/lymphoma virus (HTLV) or had antibodies against HTLV antigens. It has previously been shown that the neoplastic cells in Japanese ATLL patients and in patients from the Caribbean are indistinguishable by morphology and marker phenotype. We now show them to be also similar with respect to their functional properties.     

An extranodal NK/T cell lymphoma,nasal type,with specific immunophenotypic and genotypic features

Extranodal NK/T cell lymphoma, 'nasal type,' is a rare clinicopathological entity in Europe. The main clinical features are nasal congestion, sore throat, dysphagia and epistaxis, due to a destructive mass involving the midline facial tissues. Pathologically, lymphoma cells exhibit angioinvasion, angiodestruction and coagulative necrosis. We report the case of a patient who presented with fever, dyspnea, nasal congestion, headache, distention of right nasal turbinates and exophytic lower leg ulcerating lesions. A CT scan of visceral scull demonstrated a filling mass of right frontal, ethmoidal and maxillary sinuses with erosion of the wall of right maxillary sinus and ventral portion of the diaphragm. A biopsy was performed in the skin lesion and showed an angioinvasive NK/T cell lymphoma CD56 negative with clonal rearrangement of the T-cell-receptor gamma gene. Up to our knowledge, this is a rare immunophenotype for NK/T-cell, 'nasal type,' lymphomas. However, the lymphoma may be classified as extranodal NK/T cell lymphoma, 'nasal type,' due to typical clinical presentation, radiologic findings and pathological characteristics of polymorphism, angioinvasion, angiodestruction and coagulative necrosis.     

Gastric mucosa-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma cell infiltration. case report

This is the first case report of gastric mucosal-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma (ATLL) cell infiltration. A 43-yr-old Japanese woman who was seropositive for antihuman T cell leukemia virus-I antibody complained of epigastric pain in April, 1996. Endoscopy showed gastric ulcers in the antrum. Biopsy specimens showed Helicobacter pylori infection. Her symptoms were relieved by treatment with ranitidine. In March, 1998, she complained of epigastric pain and abdominal fullness. Smears of peripheral blood revealed atypical lymphocytes with nuclear irregularity, consistent with ATLL cells. She was diagnosed to have ATLL. Endoscopy revealed multiple gastric ulcers in the antrum and the angle. Biopsy specimens demonstrated small centrocyte-like cells forming lymphoepithelial lesions, with infiltrations of large atypical lymphoid cells of ATLL. On immunohistochemical staining, the small centrocyte-like cells were positive for B cell markers (L26, CD20), whereas the large atypical lymphoid cells were positive for T cell marker (UCHL-1, CD45RO). Her findings were attributed to gastric mucosal-associated lymphoid tissue lymphoma with gastric involvement with ATLL.     

Marker profiles of human leukemia and lymphoma cell lines

Summary By means of the multiple marker analysis, a total of 55 human leukemia-lymphoma cell lines which included 15 T-cell, 30 B-cell, four myelomonocytic-cell, and six non-T, non-B cell lines was characterized for their marker profiles. The multiple markers used included a number of cell surface markers as detected by either rosette or immunofluorescence tests, enzyme assays, cytogenetic analysis, and certain functional assay. Based on the criteria previously defined it was found that all the cell lines were proved to represent original leukemia-lymphoma of ALL, AML, CLL, CML in blastic phase or variety of lymphomas. The monoclonality, a frozen state at a specific stage of differentiation-maturation, and cytogenetic marker in each leukemia-lymphoma cell line were remarkable common properties and were stable for years of cultivation. Similar, if not identical, general characteristics were observed in the study on 344 cases of uncultured fresh leukemia-lymphomas by the multiple marker analysis. While no single marker specific to any type of tumor was found, the study offers not only a basis for better understanding of the biology of leukemia-lymphoma but also an insight into normal hematopoietic cell differentiation in man.Supported by USPHS grants CA-14413, CA-17609, CA-25865, AI-08899, and contract 31-CB74165 from the National Cancer Institute and National Institute of Allergy and Infectious Diseases     

Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus

We established an interleukin 2 (IL-2)-dependent human T cell line, Kit 225, from a patient with T cell chronic lymphocytic leukemia (T-CLL) with OKT3+, -T4+, -T8- phenotype. Southern blot analysis showed that Kit 225 is not infected with human T cell leukemia/lymphoma virus (HTLV) type I or II, and is probably derived from the major clone in the fresh leukemic cells. Kit 225 cells express a large amount of IL 2 receptors constitutively and their growth is absolutely dependent on IL 2. No other stimuli, such as lectins or antigens, are required for maintaining the responsiveness to IL 2. As abnormal IL 2 receptor expression was also seen originally in the fresh leukemic cells, the establishment of this cell line with IL 2 suggests that IL 2-mediated T cell proliferation is involved in the leukemogenesis of some cases of HTLV-negative T-CLL.     

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation

Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.     

T-lymphocyte cell lines derived from patients with acute lymphoblastic leukemia.

Several lymphoid cell lines with thymus-dependent lymphocyte (T-cell) characteristics have been established from 2 patients with acute lymphoblastic leukemia (ALL). These cell lines are considered to be leukemic T-cells on the basis of their abnormal chromosome constitution, growth in heterologous animals, ability to form rosettes with sheep red blood cells and the absence of immunoglobulin production, and destruction by antithymus cell sera. Sera from patients with leukemia did not react with these cultured cells but there was a strong reaction with infectious mononucleosis sera despite the fact that the cultured leukemia T-cells had no detectable Epstein-Barr virus (EBV) nor its genome.     

Cytogenetic studies on prolymphocytic leukemia. II. T cell prolymphocytic leukemia

We report chromosome abnormalities in 15 cases of T cell prolymphocytic leukemia (T-PLL). All cases were characterized by clinical, morphological, and membrane marker analysis. The most frequent abnormality was an inv(14)(q11q32) observed in nine cases. The T cell receptor (TCR) alpha chain gene is localized to 14q11 and the immunoglobulin heavy-chain gene to region 14q32. Four cases also had translocations involving 14q11. Trisomy or multisomy for 8q resulting from an i(8q) or from rearrangements with 8p12 as the breakpoint was observed in nine cases, and a deletion of 6q was found in four cases. Trisomy or partial trisomy for 7q was observed in four cases, of which two had abnormalities of band 7q35 to which the TCR beta chain gene is mapped. The expression of Tac antigen, investigated in 27 cases of human T cell leukemia virus I-negative chronic T cell leukemia, which included the 15 cases of T-PLL, showed a good correlation with abnormalities of 7q35. Our studies on chronic T leukemias suggest that inv(14)(q11q32) and trisomy for 8q are abnormalities characteristic of T-PLL.     

Clinical, immunophenotypic and cell cyclic analysis in chronic lymphocytic leukemia

15 cases of chronic lymphocytic leukemia (CLL) were immunophenotyped with a panel of monoclonal antibodies. 13 cases were B-CLL, which was characterized by CD20+, HLA-Dr+, SmIg+ and CD5+/Em+. 2 cases were T-CLL, one with Ts phenotype and HLA-Dr+ T-Cll in the other. The ratio of G0 + G1 cells in bone marrow of CLL was 91.1 +/- 2.3% (76.0 +/- 5.1% in controls), while S + G2M cells was 8.9 +/- 2.3% (23.9 +/- 5.1% in controls). The ratios of various cyclic cells were similar in bone marrow and in peripheral blood. Prolymphocytoid transformation developed in the late stage in 3 CLL patients. The clinical course, cytochemistry and immunologic changes in CLL were also analysed.     

Phenotypic and functional analysis of leukemic cells from 16 patients with adult T-cell leukemia/lymphoma

Surface phenotypes of leukemic cells from 16 patients with adult T-cell leukemia/lymphoma (ATLL) were analyzed by using monoclonal antibodies (anti-Leu-1, anti-Leu-2a, anti-Leu-3a, anti-HLA-DR and MAS 036 c), and the effect of leukemic cells on PWM-induced normal B-cell differentiation was also studied. The majority of ATLL cells bear Leu-1 and Leu-3a antigen on cell surface but lack Leu-2a antigen and were unreactive with MAS 036 c. These results indicate that ATLL cells are of peripheral inducer/helper T-cell origin. However, contrary to the surface phenotype, ATLL cells from 10 patients showed potent suppressor activity on PWM-induced normal B-cell differentiation to immunoglobulin- producing cells (Ig-PC) and no case showed helper activity. The dissociation between surface phenotype and function of ATLL cells is discussed in this article.     

Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation

Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.