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Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.

A variety of cytokines mediate the activation of Janus protein tyrosine kinases (Jaks). The Jaks then phosphorylate cellular substrates, including members of the signal transducers and activators of transcription (Stat) family of transcription factors. Among the Stats, the two highly related proteins, Stat5a and Stat5b, are activated by a variety of cytokines. To assess the role of the Stat5 proteins, mutant mice were derived that have the genes deleted individually or together. The phenotypes of the mice demonstrate an essential, and often redundant, role for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin. Conversely, the responses to a variety of cytokines that activate the Stat5 proteins, including erythropoietin, are largely unaffected.

The Friend virus susceptibility 2 (Fv2) locus encodes a dominant host factor that confers susceptibility to Friend virus-induced erythroleukaemia in mice. We mapped Fv2 to a 1.0-Mb interval that also contained the gene (Ron) encoding the stem cell kinase receptor (Stk). A truncated form of Stk (Sf-stk), which was the most abundant form of Stk in Fv2-sensitive (Fv2ss) erythroid cells, was not expressed in Fv2 resistant (Fv2rr) cells. Enforced expression of Sf-stk conferred susceptibility to Friend disease, whereas targeted disruption of Ron caused resistance. We conclude that the Fv2 locus encodes Ron, and that a naturally expressed, truncated form of Stk confers susceptibility to Friend virus-induced erythroleukaemia.

The murine transcription factor murine cyclin D-binding Myb-like protein (mDmp1) arrests the cell cycle in G 1 phase, through an activity that can be overridden by direct interaction with the D-type cyclins. Here, we describe the identification, sequence, chromosomal localization, and expression of the human cognate, hDMP1 . The hDMP1 cDNA contains a 2280 bp open reading frame that shares a high degree of identity with the mDmp1 coding region. The 4.4 kb hDMP1 messenger RNA is ubiquitously expressed in normal human tissues, with highest levels in testis and substructures within the brain. By use of fluorescence in situ hybridization with a human genomic P1 probe, we assigned hDMP1 to chromosome 7, band q21. This chromosomal region is frequently deleted as part of the 7q-minus and monosomy 7 abnormalities of human acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We analyzed hDMP1 copy number by fluorescence in situ hybridization in leukemic blasts from nine patients with abnormalities of the long arm of chromosome 7, and in each case one allele of the hDMP1 gene was deleted. Functional analysis of the mDmp1 protein has shown that it negatively regulates cell proliferation, which suggests that this gene is a candidate suppressor of malignant transformation. Further study will be needed to determine whether gene-specific mutations implicate hDMP1 as a tumor suppressor in acute leukemias with deletions of the long arm of chromosome 7 or in other types of human malignancy.

We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children.

A variety of cytokines activate receptor-associated members of the Janus family of protein tyrosine kinases (Jaks). To assess the role of Jak2, we have derived Jak2-deficient mice. The mutation causes an embryonic lethality due to the absence of definitive erythropoiesis. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fail to respond to erythropoietin, thrombopoietin, interleukin-3 (IL-3), or granulocyte/macrophage colony-stimulating factor. In contrast, the response to granulocyte specific colony-stimulating factor is unaffected. Jak2-deficient fibroblasts failed to respond to interferon gamma (IFNgamma), although the responses to IFNalpha/beta and IL-6 were unaffected. Lastly, reconstitution experiments demonstrate that Jak2 is not required for the generation of lymphoid progenitors, their amplification, or functional differentiation. Therefore, Jak2 plays a critical, nonredundant role in the function of a specific group of cytokines receptors.

In some cases, bone marrow aplasia has been thought to result from immunologic abnormalities. Our patient had severe transfusion-dependent aplastic anemia, which responded to treatment with prednisone on two occasions. The exacerbations of aplastic anemia were associated with lymphocytic proliferation which on one occasion had the characteristics of T-cell chronic lymphocytic leukemia. Though he had had mild lymphoproliferation for a number of years, he ultimately died with progressive diffuse lymphoid infiltration of the bone marrow and other organs. The simultaneous occurrence of the T-cell lymphoproliferation and aplastic anemia and their simultaneous response to therapy suggests that this may be a clinical example of T-lymphocyte mediated suppression of erythropoiesis.

The symptoms and clinical courses of 4 patients with neurofibromatosis and lesions of the brain stem identifiable on computed tomographic and/or magnetic resonance imaging scans are described. Two patients underwent biopsy and both had low-grade astrocytomas with no evidence of anaplasia. Both received radiation and chemotherapy. The other 2 patients have been monitored without biopsy or treatment. Three patients are alive and clinically stable, having been followed up for an average of 4 years; neuroimaging studies have shown no change in their tumors. The fourth patient died of a supratentorial primitive neuroectodermal tumor. Imaging studies had shown no change in his brain stem lesion, which at autopsy was found to be a focal collection of fibrillary astrocytes. These data suggest that some patients with brain stem lesions and neurofibromatosis may have a prognosis distinctly different from that of the typical patient with a brain stem glioma. We recommend caution against aggressive operative and adjuvant therapy for brain stem lesions in patients with neurofibromatosis, unless progression of the lesion is documented clinically and/or by imaging.