David L. Morgan

Macrophage Activation and Immunomodulation by Myeloperoxidase

Abstract Myeloperoxidase (MyPo) is an enzyme found in neutrophils and monocytes that plays an important role in the microbicidal and cytocidal activities of these cells. The present studies show that this enzyme can also affect both capacities and functions of macrophages. When resident peritoneal macrophages from C57BL/6 mice were exposed to preparations of either human or canine enzyme in vitro, tumor necrosis factor (TNF) was released. The amount of TNF produced was dose dependent and could be neutralized with polyclonal anti-TNF. Low levels of interferon were also produced by these cells. In addition, exposure of murine macrophages in vitro to this enzyme resulted in increased ability to destroy 3T12 target cells. Intravenous injection of mice with myeloperoxidase induced the production of both TNF and interferon, which could be detected in the sera. Possible mechanisms of TNF induction include radical production by myeloperoxidase or ligand-receptor interaction by the binding of this enzyme to the mannosyl-fucosyl receptor. These results, when taken in their entirety, suggest that this enzyme can modulate the immune response through effects on macrophage function.

Myeloperoxidase-positive Intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma (IVLBL) is an uncommon form of non-Hodgkin lymphoma that is also known as malignant angioendotheliosis, intravascular lymphomatosis, and angiotropic large-cell lymphoma. The disease is characterized by a bizarre population of neoplastic cells, which are found systemically within vascular lumina. Although originally thought to be a neoplastic process of the endothelial cells, it has since been demonstrated, by molecular techniques and immunohistochemistry, that the neoplastic cells are of lymphoid origin. The differential diagnosis of these lesions includes granulocytic sarcomas that can be distinguished from IVLBL or other lymphomas by the presence of immunohistochemical positivity for myeloperoxidase. We describe a patient with a history of a myelodysplastic syndrome who subsequently developed IVLBL, which demonstrated immunohistochemical positivity for myeloperoxidase. To our knowledge, this represents the first case of a malignant lymphoma to demonstrate such findings.

Interstitial deletion of 20q in a patient with Waldenström macroglobulinemia following chemotherapy

A 76-year-old male with a history of renal insufficiency was found to have anemia, an IgM kappa paraprotein on serum immunofixation studies, absence of lytic bone lesions, and findings in the bone marrow consistent with Waldenström macroglobulinemia (WM). Cytogenetic studies including fluorescence in situ hybridization (FISH) on the post-treatment bone marrow revealed the karyotype 46,XY,del(20)(q13.1q13.3). Less than 70 cases of karyotypic abnormalities in patients with WM have been reported, which have shown no abnormalities specific to WM. Monosomy or trisomy of chromosome 20 has been reported in approximately eight cases, but to our knowledge this is the first case report of an interstitial deletion of 20q, confirmed by FISH using chromosome 20 subtelomeric specific probes. Interstitial deletions of 20q are known to occur in polycythemia vera and other hematological malignancies, especially those of myeloid origin.

Translocation t(15;17) in acute myelogenous leukemia with atypical megakaryoblastic features: Diagnostic, clinical, and therapeutic implications

We describe the first reported case of acute myelogenous leukemia with characteristics of megakaryoblastic differentiation and the t(15;17) chromosomal translocation, which has been associated with promyelocytic leukemia. The diagnostic, clinical, and therapeutic implications are discussed.

Molecular Cytogenetic Characterization of a Recombinant Chromosome rec(22)dup(22q)inv(22)(p13q12.2)

Pericentric inversions occur at a frequency of 0.12–0.7% in humans. However, pericentric inversions of chromosome 22 appear to be common, especially in patients originating from the Guadalajara region of Mexico. Here, we report a seventh case of a pericentric inversion of chromosome 22, the resulting recombinant chromosome, and describe the phenotypic features associated with such a recombinant chromosome. It is interesting that five of the seven patients with inv(22) come from Mexico, and four of the five patients from the Guadalajara region.

Translocation (X;14)(p11;q32) in a patient with refractory anemia

Abstract We describe an unusual translocation, t(X;14)(pl1;q32), in a patient with refractory anemia of myelodysplastic syndrome.

Development of minimally differentiated acute myeloblastic leukemia with novel isochromosome 18p and antecedent aplastic anemia

We describe a case of acute myeloblastic leukemia with a novel isochromosome 18, i(18)(p10), preceded by aplastic anemia for six months. The patient is a cotton grower chronically exposed to pesticides. The significance of this chromosomal abnormality is unknown. The possible relationship to the preceding history of aplastic anemia and occupational pesticide exposure is speculated on. The possible mechanism of the association of acute leukemia and aplastic anemia is discussed.