Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis

We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6 deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment

Epstein-Barr virus-positive recipient type B-cells survive in a "complete chimera" after allogeneic bone-marrow transplantation

Latency of Epstein-Barr virus infection may be generated by surviving immortalized B cells or by continuous re-infection. EBV-positive B-cell tumors have been found following bone-marrow transplantation (BMT) and were of donor type in the few cases investigated. We established a B-cell line from the bone marrow of a patient in complete remission following allogeneic BMT for aplastic anemia 18 months post-grafting. Differences in sex and isoenzymes allowed an exact determination of chimerism in our case. While the patient showed persistent complete chimerism of all cell lineages, cells grown in culture were of recipient type. They expressed B-cell markers, showed a monoclonal rearrangement of the immunoglobulin genes and carried EBV-associated antigens. As direct preparations of cells from the patient did not contain detectable recipient-type cells, it appeared likely that small numbers of EBV-transformed B cells of the recipient survived for long periods in this patient. For the development of secondary B-cell neoplasms in vivo, additional patho-physiological steps like severe graft versus host disease or T-cell suppression are obviously required because the patient was still free of lymphoma 3 years post-grafting

Inhibitory effect of extracellular purine nucleotide and nucleoside concentrations on T cell proliferation.

The release of nucleic acids and derivatives after tissue-injury may affect cellular immune-response. We studied the impact of extracellular ribo-, desoxyribonucleotides and nucleosides on T-cell immunity. Peripheral-blood-mononuclear-cells (PBMCs) or isolated CD3(+)T-cells obtained from 6 healthy donors were stimulated via CD3/CD28 Dynabeads or dendritic cells (DCs) in the presence or absence of pyrimidine-, purine-nucleotides and -nucleosides (range 2-200µM). Addition of deoxy-, guanosine-triphosphate (dGTP, GTP) and guanosine resulted in a partial inhibition of the induced T-cell-proliferation. Adenosine-triphosphate (ATP), adenosine and the pyrimidine-ribo- and -deoxyribonucleotides displayed no inhibitory capacity. Inhibitory effects of dGTP and GTP, but not of guanosine and ATP were culture-media-dependent and could be almost abrogated by use of lymphocyte-culture-media Xvivo15 instead of RPMI with standard-supplementation. In contrast to RPMI, Xvivo15 resulted in a significant down-regulation of the cell-surface-located ectonucleotidases CD39 (Ecto-Apyrase) and CD73 (Ecto-5´-Nucleotidase), critical for the extracellular nucleotides-hydrolysis to nucleosides, explaining the loss of inhibition mediated by dGTP and GTP, but not Guanosine. In line with previous findings ATP was found to exert immunosuppressive effects on T-cell-proliferation. Purine-nucleotides, dGTP and GTP displayed a higher inhibitory capacity, but seem to be strictly dependent on the microenvironmental conditions modulating the responsiveness of the respective T-lymphocytes. Further evaluation of experimental and respective clinical settings should anticipate these findings

Chrysoberyl recovered with Sapphires in the New England placer deposits, New Southwales, Australia

Mineralogical, chemical, and spectroscopic properties of chrysoberyl crystals recovered from sapphire placer deposits, related to Tertiary volcanic rocks, in the New England gem fields in New South Wales (NSW), Australia, are presented. The samples appeared yellow, yellowish brown, or brown in transmitted light, and some crystals revealed a distinct sectorial zoning between brown i (011) and yellow o (111) growth areas. In reflected light, the i sectors showed a whitish appearance, and cabochon-cut samples with larger whitish i sectors displayed chatoyancy. On the basis of morphological properties, trace-element contents, and absorption spectra, the chrysoberyl samples were subdivided into four different groups, possibly originating from different host rocks. The largest such group, comprised of samples with distinct sectorial color zoning, also revealed a pronounced variation in trace-element levels of titanium, niobium, and tantalum between the different growth sectors. Smaller variations were found for boron, magnesium, and iron, and almost no variation was observed for gallium