Russel E. Kaufman

Hodgkin's disease presenting as myelofibrosis.

Four patients with Hodgkins disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkins disease is reviewed. Hodgkins disease should be considered in the differential diagnosis of idiopathic myelofibrosis.

Expression of the CD7 Ligand K-12 in Human Thymic Epithelial Cells: Regulation by IFN-γ

CD7 is an immunoglobulin superfamily molecule expressed on T, NK, and pre-B lymphocytes. Previous studies have demonstrated a role for CD7 in T- and NK-cell activation and cytokine production. Recently, an epithelial cell secreted protein, K12, was identified as a CD7 ligand. Although CD7 is expressed intrathymically, it is not known if K12 is produced in human thymus. To determine roles that K12 might play in the human thymus, we analyzed expression of K12 in human thymocytes, thymic epithelial cells (TE), and thymic fibroblasts. We found that recombinant human K12 bound strongly to soluble hCD7, with a Keq of 37.6×10–9M, and this interaction was inhibited by a novel antihuman K12 monoclonal antibody (K12-A1). K12 mRNA was detected by RT–PCR and northern analysis in human TE and thymic fibroblasts, but not in human thymocytes. Expression of K12 in TE cells was upregulated by IFN-γ . Taken together, these data demonstrated that K12 is produced by human TE cells and thymic fibroblasts, and is regulated in thymus by IFN-γ . These data suggest a role for thymic microenvironment-produced K12 in regulation of thymocyte signaling and cytokine release, particularly in the setting of thymus pathology where IFN-γ is upregulated such as myasthenia gravis.

Chronic Granulocytic Leukemia in a Patient with Sickle Cell Anemia

R eports of patients with sickle cell disease and hematologic neoplasms are rare, although there is no evidence that patients with sickle cell disease have increased resistance to such malignancies. It has been speculated that the rarity of hematologic neoplasms in sickle ce!l disease is due to early mortality in this disease. Although reported rarely, sickl’e cell disease has been found to co-exist with multiple myeloma, Hodgkin’s disease, malignant histiocytosis, acute myelocytic leukemia, acute myelomonocytic leukemia, acute lymphocytic leukemia, and chronic granulocytic leukemia [l]. There are, to our knowledge, two previous descriptions of patients with sickle cell anemia and chronic granulocytic leukemia [2,3], and one report of a patient with sickle/beta thalassemia and chronic granulocytic leukemia [4].

The mouse CD7 gene: identification of a new element common to the human CD7 and mouse Thy-1 promoters

Abstract Human CD7 (hCD7) is a 40 000 Mr member of the immunoglobulin gene superfamily that is expressed early in natural killer (NK) and T-lymphocyte development. CD7 is involved in lymphocyte activation, as ligation of CD7 activates NK and TCRγδ T lymphocytes, and ligation of CD7 on TCRαβ T lymphocytes induces a non-mitogenic calcium flux. We have previously cloned and characterized the gene for human CD7 (hCD7) and have described its expression in transgenic mice. Recently a mouse cDNA homologous to hCD7 was reported, which we mapped to the corresponding mouse chromosomal location as hCD7. We now report the identification and characterization of a mouse CD7 (mCD7) genomic clone. We demonstrated that the mCD7 gene was similar both in size and structural organization to hCD7. Comparison of the 5′ flanking sequences of the mCD7 and hCD7 genes revealed two regions of sequence similarity. Electrophoretic mobility shift assay confirmed both of these regions to be sites of tissue-restricted protein binding in vitro. The more 3′ similarity region also shared sequence with a region in the mouse Thy-1 gene 5′ flanking region, suggesting that this sequence may be a cis-acting regulatory element common to all three genes. Thus, the promoter regions and exonic organization were similar in the human CD7, mouse CD7, and mouse Thy-1 genes.

Inclusion of a sensitivity control to add a quality-control parameter and improve reproducibility in BCR, immunoglobulin, and T-cell receptor gene-rearrangement studies.

Molecular analyses to determine clonality of T and B cells in malignant lymphoma and leukemia and to detect the (9;22) translocation in chronic myelogenous leukemia are commonly used in clinical molecular biology laboratories. We describe the inclusion of a sensitivity control in each of these assays derived from DNA of well-characterized cell lines. The inclusion of such a sample adds an important quality-control parameter to ensure assay-to-assay reproducibility and to satisfy accreditation and regulatory requirements.