Giovanni Emilia

Lymphocytes and low-frequency electromagnetic fields.

Human lymphocytes have been used by several researchers to investigate the biological effect of electromagnetic fields (EMF). EMF modulate the response by lymphocytes to lectin stimulation. The size and direction of the effect depends both on the lymphocyte physiology and on the physical parameters characterizing the EMF. Lymphocytes have also been used to investigate the genotoxicity of EMF exposure.— Cadossi, R.; Bersani, F.; Cossarizza, A.; Zucchini, P.; Emilia, G.; Torelli, G.; Franceschi, C. Lymphocytes and low‐frequency electromagnetic fields. FASEB J. 6: 2667‐2674; 1992.

Additional neoplasms and HCV infection in low-grade lymphoma of MALT type

Several chronic inflammatory conditions and genetic alterations are likely to be involved in the pathogenesis of low‐grade lymphoma of MALT type. In a well‐characterized series of 27 patients with low‐grade lymphoma of MALT type, we studied: (1) the incidence of other neoplasms, which might be indicative of genetic instability, apparently a characteristic of this disease; (2) the prevalence of serologic and molecular markers of HCV infection, which has been found in association with other lymphoproliferative disorders. Three patients had one or more additional cancers; a total of eight tumours, five of which occurred in the same patient, suggests the presence of some genetic instability in at least some cases of the disease. Rather unexpectedly, anti‐HCV antibodies and HCV RNA sequences were documented in 50% of the patients examined, without elevation of serum transaminases. Of interest, the two patients with parotid and conjunctival MALT lymphomas, respectively, with a previous history of Sjögrens syndrome, were HCV positive. We suggest, for the first time, that HCV may be considered, in addition to Helicobacter pylori, as another potential infectious co‐factor in the multistep pathogenesis of low‐grade lymphomas of MALT type.

Long-term salvage treatment by cyclosporin in refractory autoimmune haematological disorders

We report on long‐term treatment (13–62 months) with cyclosporin A (CyA) in eight patients with autoimmune haematological disorders, resistant to all usual therapies. Three patients had an autoimmune haemolytic anaemia (AHA); four an idiopathic thrombocytopenic purpura (ITP), and one an Evans syndrome. All patients were responsive: six achieved complete remission and two partial remission. The side‐effects were moderate and transient. The majority of surviving patients remain dependent on continued drug administration. The CyA appears to be recommendable as a salvage treatment in life‐threatening, resistant autoimmune haematological diseases.

Genomic Instability and Aging

In previous papers we proposed the general hypothesis that aging and longevity are the result of a balance between mechanisms that favor aging and mechanisms that counteract the aging The mechanisms favoring aging and senescence are those that cause damage to macromolecules and other body components. They come from both exogenous and endogenous sources. Ionizing radiation, UV radiation, and xenobiotics, including dietary carcinogens, are the most common exogenous genotoxic compounds with which we cope in everyday life. Body heat, oxygen free radicals, glucose, and other oxidative sugars are representative of the byproducts of a variety of metabolic pathways and represent unavoidable, potentially genotoxic agents3

Cytogenetic conversion in a case of polycythaemia vera treated with interferon-alpha.

Summary Polycythaemia vera is a clonal disorder of the haemopoietic stem cell causing a pathologic expansion of the erythroid and sometimes the megakaryocytic and myeloid elements. In order to avoid the possible mutagenic effects of radioactive phosphorus, alkylating agents and hydroxyurea, since 1988 α‐IFN has been used for the treatment of PV and has been shown to induce and maintain haematological remission. We describe a 24‐year‐old PV patient with chromosomal abnormalities who achieved not only a reduction of the proliferation of erythroid elements and reticulin content in the bone marrow, but also a complete cytogenetic remission after IFN treatment.

Cellular levels of mRNA from c‐myc, c‐myb and c‐fes onc‐genes in normal myeloid anderythroid precursors of human bone marrow: an in situ hybridization study

Summary. The expression of three onc‐genes, c‐myc, c‐myb and c‐fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by ‘in situ’ hybridization with tritium‐labelled probes. A relatively large amount of m‐RNA from the three onc‐genes was detected in myeloblasts and promyelocytes, but whereas the expression of c‐myb and c‐myb decreased in more advanced stage of maturation of the myeloid lineage, c‐fes mRNA remained at a relatively high level until the granulocyte stage, c‐myc and c‐myb were expressed at a fairly high level in basophilic erythroblasts, which also showed low levels of c‐fes mRNA. No expression of these onc‐genes was detectable in more mature erythroblasts, Megakaryocytes showed high levels of m‐RNA from all three onc‐genes.

Progression of Essential Thrombocythemia to Blastic Crisis Via Idiopathic Myelofibrosis

We report a 61-year-old man with essential thrombocythemia (ET) whose clinical course was followed for 12 years. The ET evolved into true idiopathic myelofibrosis (IM) 6 years after the initial diagnosis and progressed to myeloid blastic transformation 6 years later. The cytogenetic analysis showed a normal karyotype during the ET phase but subsequent analysis revealed an abnormal karyotype during the IM phase which evolved clonally at blastic crisis with constant involvement of chromosome 13q and chromosome 7. The close monitoring of essential events, using clinical, morphologic, immunologic and cytogenetic parameters, allowed us to carefully identify the transition from one chronic myeloproliferative disease (MPD) to another. This is only the second case reported showing a clinical evolution of this nature. The clinical and biological aspects of the disease are briefly discussed.

Sinus Histiocytosis with Massive Lymphadenopathy

To date, the morphological aspects of sinus histiocytosis with massive lymphadenopathy (SHML) have been fully described. The disease is characterized by an enlargement of lymph nodes in which the sinuses are dilated and infiltrated by histiocytes, often phagocytosing lymphocytes. Even if the prognosis is usually benign and not requiring therapy, several fatal cases have been reported. The etiology is still obscure and the biology is not yet completely clear. Recent immunophenotypical studies suggest that histiocytes may belong to the T-zone associated histiocyte lineage. They may be cytologically homogeneous, but can express different antigenic patterns according to their stage of differentiation. Cytogenetic and molecular aspects of the disease have only been sporadically investigated. In order to better understand the pathogenesis of SHML, which seems to be a disorder lying in between the fields of infections, immunological disease and neoplasia, it is considered very useful to systematically employ a variety of immunophenotypical, cytogenetic and molecular techniques to study the disease, particularly in cases which are clinically atypical or with a more aggressive evolution.

Overexpression of c-kit in a leukemic cell population carrying a trisomy 4 and its relationship with the proliferative capacity.

The expression of c-kit and its ligand, the stem cell factor (SCF), was studied in five cases of acute myeloid leukemia. One of these had a trisomy of chromosome 4, where the c-kit oncogene is located. In this case, the c-kit oncogene was overexpressed, but matched by a low expression of its ligand, SCF. The molecular evaluation of the growth rate by c-myc and the histone H3 expression indicated that the growth fraction of this cell population was very low. In one of the other leukemic cell populations studied, characterized by a low expression of c-kit and an elevated expression of the SCF, the growth fraction was also very low. Our results suggest that at least for some receptor oncogenes, the simple overexpression cannot be taken as an indication that the oncogene is involved in the deregulation of cell proliferation.

Lymphoid blastic crisis at the onset of chronic granulocytic leukemia: report of two cases.

Two patients with a typical hematologic pattern of acute lymphatic leukemia were brought into complete remission by treatment. A few weeks later they developed a typical peripheral and bone marrow pattern of chronic granulocytic leukemia, with Philadelphia chromosome and very low leukocyte alkaline phosphatase. These cases, along with other findings recently reported in the literature, support the possibility of a previously unrecognized relationship between lymphoblastic cell populations and chronic granulocytic leukemia. Cancer 40:865–870, 1977.