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The apicomplexan parasite Toxoplasma gondii must invade host cells to continue its lifecycle. It invades different cell types using an actomyosin motor that is connected to extracellular adhesins via the bridging protein fructose-1,6-bisphosphate aldolase. During invasion, aldolase serves in the role of a structural bridging protein, as opposed to its normal enzymatic role in the glycolysis pathway. Crystal structures of the homologous Plasmodium falciparum fructose-1,6-bisphosphate aldolase have been described previously. Here, T. gondii fructose-1,6-bisphosphate aldolase has been crystallized in space group P22121, with the biologically relevant tetramer in the asymmetric unit, and the structure has been determined via molecular replacement to a resolution of 2.0 Å. An analysis of the quality of the model and of the differences between the four chains in the asymmetric unit and a comparison between the T. gondii and P. falciparum aldolase structures is presented. [ABSTRACT FROM AUTHOR]

An unusual case of malignant peripheral nerve sheath tumor (MPNST) arising in the posterior mediastinum of a 59-year-old man is reported. Histopathologically, the tumor showed an admixture of a dense proliferation of small round cells resembling a primitive neuroectodermal tumor (PNET) and a pleomorphic spindlle cell sarcomatous area. Abortive rosettes, primitive neural tube-like structures, and a few glandular structures were found in the small round cell area. Small round cells were immunoreactive for neural cell adhesion molecule and synaptophysin, but were not immunoreactive for MIC2 and neuron-specific enolase. Pleomorphic spindle cells were occasionally arranged in a storiform pattern and were diffusely immunoreactive for S-100 protein. The MPNST of small round cell type is distinguishable from PNET by its negative immunoreactivity for MIC2, and the present tumor is assumed to be derived from primitive neuroectodermal cells in the peripheral nerve capable of bidirectional (neuron and Schwann cell) differentiation. [ABSTRACT FROM AUTHOR]

Primitive neuroectodermal tumors (PNET) occur either in the central nervous system (CNS; central PNET, cPNET) or in the peripheral sites (peripheral PNET, pPNET). Recent molecular approaches have been defining a new concept of PNET, that is, the pPNET including Ewing's sarcoma (ES) which expresses MIC2 glycoprotein and shows the specific chimeric gene of EWS-FLI1. The expression of MIC2 and the genetic rearrangement of EWS-FLI1 are considered to be highly specific to the pPNET/ES. This study examined the expression of MIC2 and EWS-FLI1 gene by means of immunohistochemistry and reverse transcriptase–polymerase chain reaction (RT-PCR) on various small round cell tumors originating in the CNS or non-CNS organs. All peripheral PNET tested expressed MIC2 and were positive for EWS-FLI1 (11/11). In contrast, all cPNET and other blastic CNS tumors were negative for MIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2), glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2). These MIC2-negative tumors were also negative for the chimeric gene product of EWS-FLI1. Interestingly, one PNET originating in the intracranial dura mater was positive for both MIC2 and EWS-FLI1 fusion gene. The results indicate that cPNET lacks any genetic or protein markers, except for a meningeal PNET which falls into the same phenotypic spectrum of pPNET. [ABSTRACT FROM AUTHOR]

We have recently shown that CD99 (MIC2) is differentially expressed during normal early B-cell development in the bone marrow (BM). Since immature B-cell precursors (BCP) are assumed to correspond to some extent to acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) cells with respect to patterns of phenotypic differentiation, we wondered whether the particular maturation-associated expression patterns of CD99 in the normal BCP stages were conserved also in malignant cells. Therefore we compared malignant and physiological B cells from paediatric ALL/NHL and normal BM samples with respect to CD99 expression using selective gating and semi-quantitative flow cytometry. Common-ALLs (n = 45) were similar to their corresponding, very immature BCPs (stage 1) in expressing very high levels of CD99. Most pre-B ALLs (n = 16) were also CD99hi and thus differed from the patterns found in normal cytoplasmic μ-chain+ (cμ+) pre-B cells (stage 2, CD99lo). In particular, we found that those pre-B-ALL cases which were CD34+ also showed higher CD99 expression than the CD34- cases. This prompted us to investigate the levels of CD99 in those rare normal BCPs which also coexpress CD34 and cμ; these cells, which are transitory from stage 1 to stage 2, were found also CD99hi, thus precisely reflecting the patterns of CD34+ pre-B ALLs. The blasts of Burkitt-type B-cell ALL/NHL samples (n = 13) expressed considerably less CD99, similarly to the more differentiated BCP stages 2 (cμ+) and 3 (surface μ-chain+). In summary, we found that paediatric B-lineage malignancies display remarkable synchrony regarding the levels of CD99 expression compared to their putative normal counterparts. [ABSTRACT FROM AUTHOR]