Dario Barbieri

3q-, 3q+ Anomaly in Malignant Proliferations in Humans

Anomalies of both No. 3 chromosomes, of the t(3q-; 3q+) type can be observed in human malignancy as reported previously. It is our experience that this anomaly is found predominantly in myeloproliferative disorders, as a rather rare event, though occurring more frequently than similar exchanges between other homologous chromosomes. Previous claims about a relationship between this anomaly and thrombocytosis could not be confirmed, but the features found in a few patients indicate that further research should be undertaken to clarify this point.

Anomalies of the long arm of chromosome 11 in human myelo- and lymphoproliferative disorders. I. Acute nonlymphocytic leukemia

In a series of 365 consecutive ANLL cases of which 45.1% had abnormal karyotypes, 13 cases were detected with a structural abnormality of the long arm of chromosome 11. Besides one isochromosome 11q, there were six deletions and six translocations. Of these 12 patients, seven had acute monocytic leukemia (FAB-type M5), two had an M4, two had an M2, and one case of secondary leukemia had an M3-like disorder. Similar results with regard to the type of leukemia were obtained upon analysis of 41 cases of ANLL with an 11q anomaly described in the literature. This study confirms that a high proportion of acute monocytic leukemias and a lesser proportion of acute myelomonocytic leukemias are characterized by an 11q anomaly, mostly involving bands q22 and/or q23. Acute monocytic leukemia with an 11q structural anomaly appears to have a poor prognosis.

High-dose bolus tirofiban and sirolimus eluting stent versus abiciximab and bare metal stent in acute myocardial infarction (STRATEGY) study--protocol design and demography of the first 100 patients.

AbstractBackground: Primary bare metal stenting and abciximab infusion are currently considered the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus eluting stents (SES), compared to bare metal stent (BMS), greatly reduce the incidence of binary restenosis and target vessel revascularisation (TVR), but their use on a routine basis results in a significant increase in medical costs. With current European list prices, the use of tirofiban instead of abciximab would save enough money to absorb the difference between SES and BMS. Aim: To assess whether in patients with STEMI the combination of SES with high dose bolus (HDB) tirofiban results in a similar incidence of major cardiovascular events (MACE) but in a lower binary restenosis rate after six months compared to BMS and abciximab. Methods and Results: 160 patients are required to satisfy the primary composite end-point, including MACE and binary restenosis. The study is ongoing: the current paper focuses on the methodology and demography of the first 100 patients so far enrolled. Patients randomised to HDB tirofiban (n = 50, mean age: 62 ± 12, 40 males) and abciximab (n = 50, mean age: 63 ± 12, 38 males) do not differ for medical history, presentation profile, medications at discharge, angiographic profile and creatine-kinase MB-fraction at peak. Conclusions: The results of the trial will be available by the end of 2004: they will be crucial for the cardiologists to know whether the gold standard for AMI treatment should be reconsidered after the introduction of SES into the clinical practice.

Involvement of chromosomes 12 and 14 in the cutaneous stage of mycosis fungoides: Cytogenetic evidence for a multistep pathogenesis of the disease

Cytogenetic studies were performed on the cells of bone marrow, peripheral blood, and skin tumor biopsies from a patient with mycosis fungoides at an early stage. Chromosome abnormalities were detected in 100% of the cells harvested from the cutaneous specimen, whereas the cells of the bone marrow and blood were karyotypically normal. Three related clones, showing increasing cytogenetic complexity, were found. Chromosome #12 was abnormal in all metaphases, and an abnormal 14q chromosome was present in a minority of cells belonging to the most complex emerging subclone. These data, along with the findings of important signs of chromosome imbalance, suggest a polyphasic evolution of this chronic T lymphoproliferative disease.

Indirect stimulation of B-cell proliferation in vitro by T cells, as evidenced by cytogenetic analysis of PHA-stimulated cell cultures of B-cell lymphomas

In a retrospective study of non-Hodgkins lymphomas, the 14q+ marker was found in at least one of the samples examined from 17 patients with B-cell lymphoproliferative diseases (LPD). In the PHA-stimulated cultures, the marker was found in each sample in 10%-100% of the cells. An indirect stimulation, as indicated by a 3H-thymidine incorporation and IG secretion, of normal B cells by a T-cell mitogen, such as PHA, has been recently documented. This phenomenon is confirmed by our chromosome analysis, which demonstrated characteristic chromosome changes in PHA-stimulated cultures of patients with B-cell malignancies and indicated that the phenomenon can be observed not only in normal B cells but also in malignant B cells.

Further cytogenetic evidence for a multistep pathogenesis of Ph-positive chronic myelogenous leukemia

A case of Ph-positive chronic myelogenous leukemia in blastic crisis was studied extensively by means of cytogenetic techniques. Karyotypic features, as well as growth patterns, kinetic data, and rates of sister chromatid exchange, were examined in bone marrow, blood, and pleural effusion cells. The data provide strong evidence for a multistep pathogenesis of the disease, the development of which appears to be linked to mechanisms of clonal selection and genetic imbalance in the malignant cell population.

Cytogenetically distinct leukemic cell lines displaying in vitro specific proliferative and differentiation capacities may account for early disease relapse in the blast phase of CML

The cytogenetic features and the proliferative and differentiation capabilities of blast cell fractions purified on a density gradient were studied in one patient with chronic myeloid leukemia (CML) in blast crisis, both at the emergence and at relapse of the disease. The results show that relapse was due to the appearance of a new leukemic cell line that was characterized by peculiar chromosomal, growth, and differentiation features, which seemingly accounted for early refractoriness to therapy and disease progression.