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G Torelli

Publications and source records attributed to G Torelli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Human herpesvirus 6 latently infects early bone marrow progenitors in vivo.

We have studied the in vivo tropism of human herpesvirus 6 (HHV-6) for hemopoietic cells in patients with latent HHV-6 infection. Having used a variety of cell purification, molecular, cytogenetic, and immunocytochemical procedures, we report the first evidence that HHV-6 latently infects early bone marrow progenitor cells and that HHV-6 may be transmitted longitudinally to cells which differentiate along the committed pathways.

Antigens, CD34↗
PubMed1999

Missense mutations in the PML/RARalpha ligand binding domain in ATRA-resistant As(2)O(3) sensitive relapsed acute promyelocytic leukemia.

BACKGROUND AND OBJECTIVE: Acute promyelocytic leukemia is characterized by the chromosomal translocation t(15;17) which yields the fusion product PML/RARa. All-trans retinoic acid probably induces differentiation of atypical promyelocytes and clinical remission in APL patients by binding to the ligand binding domain (LBD) of the RARa portion of the PML-RARa chimeric protein. Structural alterations of the LBD of the PML/RARa have been revealed in ATRA-resistant APL cell lines and in a few APL patients with acquired clinical resistance to ATRA therapy. Two APL relapsed patients with clinical resistance to ATRA therapy were evaluated for the presence of nucleotide mutations in the LBD of PML/RARa gene and then treated with arsenic trioxide (As2O3). DESIGN AND METHODS: DNA fragments from the LBD of the PML/RARa chimeric transcript were obtained by reverse-transcribed polymerase chain reaction. Direct sequencing was performed by an unambiguous bi-directional automatic analysis. Samples representative of APL onset and relapse were analyzed from both patients. RESULTS: In both patients, at the ATRA-resistant relapse, a missense point mutation in the LBD of the PML/RARa gene was found. The mutations, absent at APL onset, led to an Arg272Gln and to an Arg276Trp amino acid substitution, according to the sequence of the RARa protein. Both patients had complete clinical and hematologic remission after treatment with As2O3. INTERPRETATION AND CONCLUSIONS: LBD missense mutations appear to be a significant mechanism of acquired ATRA-resistance in vivo, closely related to clinical APL relapse. The two cases reported here provide the first in vivo evidence of APL relapsed patients, who have become ATRA-resistant for molecular reasons, being sensitive to arsenic trioxide.

Adult↗
PubMed1998

Absence of a directly causative role for human herpesvirus 7 in human lymphoma and a review of human herpesvirus 6 in human malignancy.

In search of a (new) viral etiological agent, we screened 64 lymph node samples from Hodgkin's disease (HD) and 43 samples (32 lymph node and 11 skin biopsies) from non-Hodgkin's lymphoma (NHL) for human herpesvirus 7 (HHV-7). Twenty-nine control samples were tested as well, including 17 with benign lymphadenopathy. None of the samples tested positive by Southern blot hybridization using HHV-7-specific probes. We conclude that there is no major HHV-7 load in human lymphoma and that HHV-7 is not likely to be directly involved in its etiology. This is in contrast to a small minority of human lymphoproliferative diseases in which HHV-6 can be found at high copy number, but in which an etiological role is still uncertain.

Herpesviridae Infections↗
PubMed1998

Expression of human herpesvirus-6 antigens in benign and malignant lymphoproliferative diseases.

Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin's lymphomas, 14 Hodgkin's disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called "mummified" Reed-Sternberg cells, in two Hodgkin's disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the virus in human lymphomagenesis. The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder.

Antigens, Viral↗
PubMed1998

Occurrence of a novel t(11;19)(q13;q13.3) in complete remission of acute promyelocytic leukemia.

A woman with t(15;17) and PML/RAR alpha positive acute promyelocytic leukemia (APL-M3v) achieved a complete remission (CR) with cytogenetic and molecular conversion, after one-month ATRA plus idarubicin treatment. During CR, less than one-month after consolidation therapy with topoisomerase II inhibitors, a novel t(11;19) (q13;q13.3) was detected in peripheral blood stem cells and later in harvest bone marrow cells. Persisting CR and the negativity for BCL1 and PRAD1 genes rearrangement, the autotransplantation was performed, with good outcome. The patient is still in CR eighteen months post-transplant, in spite of the persistence of a small t(11;19) clone in BM cells. The emergence of a novel chromosomal change during CR of acute leukemia is a rare phenomenon. This is the first t(11;19)(q13;q13.3) described in APL. This finding raises the issue of whether the abnormal karyotypes at remission might represent a risk of tumor recurrence. The meaning of this genomic instability is yet unknown.

Antineoplastic Agents↗
PubMed1998

Chronic myeloid leukemia with thrombocythemic onset may be associated with different BCR/ABL variant transcripts.

Ph-positive chronic myeloid leukemia (CML) mimicking essential thrombocythemia (ET) at onset seems to be a distinct clinical entity. Whether this rare clinical form of CML is associated with single, specific variants of BCR/ABL transcripts is a matter of debate. Among 82 consecutive patients with Ph-positive CML, we identified 3 patients in which the disease mimicked ET at presentation, because of marked thrombocytosis and moderate leukocytosis, with few immature myeloid cells in peripheral blood and blood basophilia in 2 of them. Molecular analysis with the reverse transcriptase-polymerase chain reaction technique showed the presence of b2a2, b3a2, and b3a2-b2a2 transcript variants in the three patients, respectively. The results of our study together with a review of literature data suggest that different BCR/ABL transcript variants may occur in CML mimicking ET, without an apparently significant prevalence of one type.

Adult↗
PubMed1998

Clinico-pathological characterization of hepatitis C virus-related B-cell non-Hodgkin's lymphomas without symptomatic cryoglobulinemia.

BACKGROUND: Epidemiological evidence has suggested an association between hepatitis C virus (HCV) infection and B-cell lymphoproliferation. We studied the prevalence of HCV infection in a series of de novo B-cell non-Hodgkin's lymphoma (B-NHL) cases and correlated virological findings with clinico-histological features. PATIENTS AND METHODS: One hundred fifty-seven patients with de novo B-NHL were included in the study. Their serum was examined by ELISA and RIBA for the presence of anti-HCV antibodies, and either the peripheral blood mononuclear cells or the pathology tissues of all of the patients were examined by reverse transcriptase polymerase chain reaction for the presence of HCV RNA sequences. RESULTS: HCV infection occurred in 22.3% of B-NHL patients and was documented before the diagnosis in about half of the positive cases. Of interest, HCV infection was more frequently found in follicular center, marginal zone and diffuse large-cell lymphoma types, but was not associated with symptomatic cryoglobulinemia. The median survival time was 48 months in HCV-positive and 52 months in HCV-negative B-NHL patients. CONCLUSIONS: Our findings strengthen the pathogenetic link between HCV and B-NHL and show that HCV infection may be associated with the malignant proliferation of defined B-cell subsets other than the immunoglobulin Mk B-cell subset involved in the pathogenesis of mixed cryoglobulinemia type II and associated lymphoplasmacytoid lymphoma type. HCV-related liver disease did not affect the survival of our B-NHL patients.

Adult↗
PubMed1998

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

Adolescent↗
PubMed1998

Human herpesvirus-8 in hematological diseases.

The huge amount of experimental and clinical observations supporting the possible involvement of human herpesvirus 8 (HHV-8) or Kaposi sarcoma herpesvirus (KSHV) in human lymphoproliferative diseases was critically reviewed during a workshop organized by the Italian Society for Experimental Hematology in Florence, Italy, on July 3rd, 1997. The organizers have prepared this report for the readers of Haematologica.

Genome, Viral↗