Biomedical subjects

G Saglio

Publications and source records attributed to G Saglio.

At least 73 records · Page 4Linked to original sources

PubMed1998

P230 BCR/ABL protein may be associated with an acute leukaemia phenotype.

The BCR/ABL rearrangement, the molecular hallmark of chronic myelogenous leukaemia (CML), is rare in acute myeloid leukaemia (AML), being detected in approximately 1% of cases. In the vast majority of CML cases the breakpoint on chromosome 22 falls in the so-called major breakpoint cluster region of the BCR gene. Only a few cases of CML with breakpoint in the minor or in the micro bcr region have so far been reported. The micro breakpoint position has been associated mainly with a mild form of CML, defined as Philadelphia chromosome-positive chronic neutrophilic leukaemia (Ph-positive CNL). Using reverse transcription-polymerase chain reaction (RT-PCR) we report a patient with an acute myeloid leukaemia phenotype at diagnosis who showed a BCR/ABL rearrangement with a breakpoint located in the micro bcr region (e19a2 junction). Cytogenetic analysis showed a progression of the malignant clone, finally leading to cells with two Ph chromosomes, trisomy 8, isochromosome 17q and deletion of the long arms of chromosome 7. The findings of chromosomal changes point to a possibility of blast crisis of CML with a clinically silent chronic phase. Immunoprecipitation and auto-phosphorylation assay revealed the expression, by the patient's blast cells, of an abnormal P230 BCR/ABL protein, which showed for the first time that this protein was constitutively activated in primary cells from patients. This finding may contribute to the understanding of the role of the BCR/ABL rearrangements in determining different leukaemia phenotypes ranging from acute lymphoid and myeloid leukaemias to mild chronic neutrophilic leukaemias.

Acute Disease↗

PubMed1998

p53 mutation in a case of blastic transformation of follicular lymphoma with double bcl-2 rearrangement (MBR and VCR).

The bcl-2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters are found in two specific regions: mbr and mcr. Rearrangements of the immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl-2 protein. In cases of rearrangement of the light chains (variant translocations), a third breakpoint has been described at the 5' part of the bcl-2 locus (vcr). In the present case, we report the molecular analysis of an FL transformed into a blastic phase unresponsive to chemotherapy. Molecular studies revealed a typical bcl-2 rearrangement at the major locus (mbr). Vcr rearrangements was also observed with only a single restriction enzyme. At the same time, SSCP analysis of exon 5 of the p53 locus disclosed an abnormal conformer. Direct sequencing revealed a point mutation at codon 163 (A --> G). Immunohistochemical analysis of the affected sites disclosed overexpression of p53 and bcl-2. It is concluded that p53 mutation can contribute to blastic transformation in cases of follicular lymphomas with double rearrangement at the bcl-2 locus (mbr/vcr).

Blast Crisis↗

PubMed1998

BCL-6 in aids-related lymphomas: pathogenetic and histogenetic implications.

AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) are classified into Burkitt's lymphoma, diffuse large cell lymphoma (DLCL), and body cavity based lymphoma. The molecular pathogenesis of AIDS-NHL is complex and involves the genetic alteration of several cancer related genes, including the BCL-6 proto-oncogene. BCL-6 encodes a zinc finger transcription factor which is selectively expressed by germinal center (GC) B-cells, but not by pre-GC or post-GC B-cells. Genetic alterations of BCL-6 occur frequently among B-cell NHL and comprise gross rearrangements as well as small mutations of the 5' noncoding region of the gene. Gross rearrangements of BCL-6 among AIDS-NHL cluster with 20% AIDS-DLCL. Conversely, mutations of the 5' noncoding region of BCL-6 occur at sustained frequency throughout the clinico-pathologic spectrum of AIDS-NHL and represent the most common genetic alteration presently detectable in these lymphomas. The frequency of BCL-6 mutations, as well as their location in the proximity of the BCL-6 regulatory regions, suggest that they may play a pathogenetic role in AIDS-related lymphomagenesis. Beside their pathogenetic implications, the occurrence of BCL-6 mutations among AIDS-NHL bears histogenetic relevance because BCL-6 mutations are regarded as a marker of B-cell transition through the GC. Thus, it is conceivable that a large fraction of AIDS-NHL is histogenetically related to GC or post-GC B-cells. This notion is further confirmed by the observation that AIDS-NHL frequently express the BCL-6 protein, which stains selectively GC B-cells throughout B-cell differentiation.

Gene Rearrangement↗

PubMed1998

Detection of bcr-abl transcript in chronic myelogenous leukemia patients by reverse-transcription-polymerase chain reaction and capillary electrophoresis.

BACKGROUND AND OBJECTIVE: Capillary electrophoresis (CE) has become an attractive alternative to SLAB gel analysis for direct and accurate detection of amplified product, and a few cycles of polymerase chain reactions (PCRs) could be sufficient for both quantitative and qualitative analysis. We try to assess: 1) whether CE could be a practical, non-isotopic method for direct detection of the presence of amplified bcr-abl obtained by a reverse transcription (RT)-PCR (qualitative analysis) and 2) whether it is possible to quantify PCR products using a competitive RT-PCR measuring peak areas of CE electropherograms (quantitative analysis). DESIGN AND METHODS: The two types of bcr-abl chronic myelogenous leukemia (CML) associated transcript products were generated by RT-PCR (qualitative analysis) from 1 microgram of total RNA extracted from bone marrow samples of 34 CML patients at diagnosis (median age 47.5; range 18-65; median Sokal's score 0.9; range 0.53-2.78). The PCR products were analyzed by SLAB-gel electrophoresis (SGE) on 2% agarose gels and by CE (128 runs; median 3.3 times for each sample). Furthermore, we assessed the amount of PCR product (quantitative analysis) by a competitive RT-PCR approach and by CE (bcr-abl transcripts were expressed as transcript per microgram of total RNA examined). RESULTS: CE separation of PCR products obtained by qualitative RT-PCR showed baseline resolution for the two peaks corresponding to the two types of bcr-abl junctions: the b2-a2 type (343 base pairs, 10 patients) was revealed at 9.33 min [standard deviation (SD) = 0.1] and the b3-a2 type (418 base pair, 24 patients) at 10.03 min (SD = 0.25). By quantitative analysis we found that there is great interpatient variability in bcr-abl expression at diagnosis: the median value of the amount of bcr-abl transcript was 78,000 bcr-abl transcript/microgram total RNA ranging from 17,300 to 750,000. The amount of bcr-abl transcript at diagnosis was related to the number of blast cells (mean value 128,859 vs. 331,722 in patients with 0% blast cells and > 1% blast cells, respectively; p = 0.004) and Sokal's score (mean value 156,865 vs. 408,800 in patients with Sokal's score < 0.8 and > 1.2, respectively; p = 0.003). INTERPRETATION AND CONCLUSIONS: Our results confirm that CE analysis offers greater resolution and enhanced sensitivity for detection and quantification of bcr-abl PCR product in the study of this leukemia. Qualitative analysis by CE of bcr-abl product provides a rapid technique (less than 20 min) for the analysis of subnanogram amounts of DNA fragments. CE run times are short, the capillary can be re-used and full automation may be feasible with data acquisition by a computer-controlled step. Competitive/quantitative analysis of bcr-abl as analyzed by CE allowed fewer reactions and more precise quantification.

Adolescent↗

PubMed1998

Evaluation of iron status in patients with chronic hepatitis C.

AIM: To evaluate the prevalence of iron overload in chronic hepatitis C and its relationship with liver histology. PATIENTS AND METHODS: Serum iron, unsaturated iron binding capacity and ferritin levels were determined in 204 consecutive anti-hepatitis C virus positive subjects, whereas hepatic iron concentration, hepatic histological grading and staging, hepatitis C virus genotypes were further assessed in a subgroup of 50 patients who underwent liver biopsy for chronic hepatitis. RESULTS: An increase in the serum markers of iron metabolism was more frequently found in subjects with aminotransferase activities above the normal range, whereas hepatic iron overload, established by direct hepatic iron determination, was found only in 9/50 (18%) patients with chronic hepatitis C. No serum iron marker could reliably predict hepatic iron stores. Patients with mild iron overload usually showed active hepatitis and fibrosis, whereas iron overload was not present in patients without fibrosis or with very mild fibrosis. Two out of nine patients with iron overload were shown to be beta thalassaemia heterozygous, and two were heterozygous carriers of a putative haemochromatosis gene mutation (His63Asp). CONCLUSIONS: Many anti-hepatitis C virus positive patients with elevated aminotransferase activities have serum ferritin levels above the normal range, but only a minority of patients with chronic hepatitis C have a mild iron overload. In chronic hepatitis C, a relationship does exist between hepatic iron content and liver fibrosis.

Analysis of Variance↗

PubMed1998

Expression of cell cycle regulatory genes in chronic myelogenous leukemia.

BACKGROUND AND OBJECTIVE: Cell cycle regulatory genes are frequently altered in a variety of malignancies. The structure and pattern of expression of eight genes involved in cell division cycle control were studied in leukemic cell samples prepared from bone marrow of patients affected by chronic myelogenous leukemia. DESIGN AND METHODS: Ten cell preparations were obtained from patients in the chronic phase, five from those in myeloid blast crisis and five from those in the lymphoid acute phase. Moreover, bone marrow CD34+ cells, purified from healthy subjects and patients with chronic myelogenous leukemia (both during chronic and acute phases), were analyzed. The investigated genes were RB1, p53 and six cyclin-dependent kinase inhibitor genes (p15INK4B, p16INK4A, p18INK4C, p21WAF1/CIP1, p27Kip1, p57Kip2). RESULTS: We found that none of these genes is structurally altered in either the chronic or acute phases, with the single exception of the p16INK4A gene, which was homozygously deleted in 1 case of lymphoid evolution. p57Kip2 expression is down-regulated during the evolution towards the blast crisis both in malignant and CD34+ cells. In addition, a significant up-regulation of p15INK4B gene expression is observable during the development of the acute phase of malignancy. INTERPRETATIONS AND CONCLUSIONS: The transcriptional modulation of some cyclin-dependent kinase inhibitors might contribute to the fatal blast crisis of chronic myelogenous leukemia.

Blast Crisis↗

PubMed1997

Association of Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma with expression of the CD138/syndecan-1 antigen.

Primary effusion lymphoma (PEL) represents a novel B-cell non-Hodgkin's lymphoma (NHL) type associated with Kaposi's sarcoma-associated herpesvirus infection and typically growing as lymphomatous effusions in the body cavities. The precise B-cell subset from which PEL originates as well as the biologic mechanisms responsible for its peculiar growth pattern are unclear. In this study, we have analyzed PEL for the expression status of CD138/syndecan-1, a molecule selectively associated with late stages of B-cell differentiation and implicated in cell-to-cell and cell-to-extracellular matrix interactions. PEL patient samples (n = 7) and cell lines (n = 5) were investigated by multiple approaches, including immunocytochemistry, flow cytometry, RNA analysis, and Western blot studies. For comparison, lymphomatous effusions other than PEL (n = 13) and tissue-based NHL (n = 103) were also tested. Expression of CD138/syndecan-1 associates at high frequency with PEL (5 of 7 patient samples and 5 of 5 cell lines), whereas it is consistently absent among other lymphomatous effusions (n = 13). The CD138/syndecan-1 isoform expressed by PEL has an average molecular weight of 420 kD, which is substantially different from that of CD138/syndecan-1 molecules generally expressed by plasma cells. These data, along with previous immunophenotypic evidence, unequivocally define that PEL cells represent a preterminal stage of B-cell differentiation and may bear implications for the peculiar growth pattern of this lymphoma.

Herpesvirus 8, Human↗

PubMed1997

Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups.

Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

Adolescent↗

PubMed1997

Cloning and gene mapping of the chromosome 13q14 region deleted in chronic lymphocytic leukemia.

Frequent deletions and loss of heterozygosity in a segment of chromosome 13 (13q14) in cases of B-cell chronic lymphocytic leukemia (CLL) have suggested that this malignancy is caused by inactivation of an unknown tumor suppressor gene located in this region. Toward the identification of the putative CLL tumor suppressor, we have constructed a high-resolution physical map of YAC, PAC, and cosmid contigs covering 600 kb of the 13q14 genomic region. In addition to densely positioned genetic markers and STSs, this map was further annotated by localization of 32 transcribed sequences (ESTs) using a combination of exon trapping, direct cDNA selection, sample sequencing of cosmids and PACs, and homology searches. On the basis of these mapping data, allelic loss analyses at 13q14 using CLL tumor samples allowed narrowing of the genomic segment encompassing the putative CLL gene to <300 kb. Twenty-three ESTs located within this minimally deleted region are candidate exons for the CLL-associated tumor suppressor gene.

Alleles↗

PubMed1997

Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas.

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHL), a major source of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals, are derived from B cells and are classified into two major categories, Burkitt's lymphoma (BL) and diffuse large cell lymphoma (DLCL). Anaplastic large cell lymphoma (ALCL) and body-cavity-based lymphoma (BCBL) represent less frequent AIDS-NHL types. The molecular pathogenesis of AIDS-NHL is characterized by distinct genetic pathways, including chromosomal rearrangements of c-MYC and BCL-6 in AIDS-BL and AIDS-DLCL, respectively. In addition to gross rearrangements, recent evidence has suggested that BCL-6 may also be affected by mutations of the gene 5' noncoding regions. Here we have investigated the distribution of BCL-6 mutations in a panel representative of all the AIDS-NHL subtypes. Forty-three AIDS-NHL were analyzed for mutations in the first exon-first intron boundary region of BCL-6. Mutations were detected in all categories of AIDS-NHL (25 of 43 cases; 58%), including 12 of 20 AIDS-BL, 10 of 15 AIDS-DLCL, two of three AIDS-ALCL, and one of five of AIDS-BCBL. BCL-6 mutations occurred independent of BCL-6 rearrangements and presence of other genetic lesions frequently associated with AIDS-NHL. These results indicate that mutations of BCL-65' noncoding regions represent the most common genetic alteration presently detectable in AIDS-NHL. The frequency of these mutations, as well as their location in the proximity of BCL-6 regulatory sequences, suggest that they may play a role in AIDS-related lymphomagenesis.

Biomarkers, Tumor↗

PubMed1997

Detection of BCL-6 rearrangements and p53 mutations in Malt-lymphomas.

Twenty-seven lymphomas of mucosa-associated lymphoid tissue (MALT) derived from distinct anatomical sites were tested for the presence of genetic lesions commonly involved in B-cell lymphomagenesis, including activation of proto-oncogenes (BCL-1, BCL-2, BCL-6, and c-MYC), disruption of tumor suppressor loci (p53, 6q), and infection by viruses [Epstein-Barr virus (EBV), and Kaposi's sarcoma-herpesvirus/human herpesvirus-8 (KSHV/HHV-8)]. Sixteen low-grade and 11 high-grade MALT-lymphomas were included in the study. The presence of genetic lesions was tested by a combination of molecular approaches, including Southern blot hybridization, polymerase chain reaction (PCR), and PCR-single strand conformation polymorphism followed by DNA direct sequencing. Alterations of BCL-1, BCL-2, or c-MYC, as well as infection by KSHV/HHV-8, scored negative in all MALT-lymphomas analysed. Conversely, rearrangements of BCL-6 and mutations of p53 clustered with a fraction of high-grade MALT-lymphomas. Deletions of 6q occurred in selected cases of both low- and high-grade MALT-lymphomas, whereas a monoclonal infection by EBV was restricted to one single patient. These data corroborate the notion that the molecular pathogenesis of MALT-lymphomas differs substantially from that of nodal B-cell lymphomas. Occasionally, however, a proportion of high-grade MALT-lymphomas may harbor selected genetic lesions among the ones commonly involved in nodal B-cell lymphomagenesis.

Blotting, Southern↗

PubMed1997

Microsatellite instability in KSHV/HHV-8 positive body-cavity-based lymphoma.

Body-cavity-based lymphoma (BCBL) is a rare non-Hodgkin-'s lymphoma (NHL) type growing in liquid phase in the body cavities. Virtually all BCBL associate with Kaposi's sarcoma-associated herpesvirus/human herpesvirus type-8 infection in the absence of molecular alterations typical of other NHL categories. Microsatellite instability (MSI), a specific variant of genomic instability frequently associated with human cancers, has not been tested in BCBL thus far. In this report, we have analyzed the presence of MSI in the tumor cells of a male patient affected by AIDS-related BCBL. The genomic configuration of 12 distinct microsatellite loci was investigated by polymerase chain reaction amplification of DNA obtained from the patient's tumor cells and from autologous peripheral blood mononuclear cells. MSI was observed at 4/12 microsatellite repeats tested. Absence of the germline allele at one microsatellite locus mapping to chromosome X indicates that, in this BCBL case, MSI represents a clonal genetic lesion affecting virtually all tumor cells. These data suggest that MSI may be potentially involved in the pathogenesis of AIDS-related BCBL.

Acquired Immunodeficiency Syndrome↗

PubMed1997

The common TEL/AML1 rearrangement does not represent a frequent event in acute lymphoblastic leukaemia occuring in children with Down syndrome.

Individuals with constitutional trisomy 21 (Down syndrome) are at increased risk of developing acute leukaemias, both of myeloid and lymphoid lineage. Although the cause of leukaemia in Down syndrome (DS) remains unknown, potential candidate genes include the ones on chromosome 21, and in particular AML1, the rearrangement of which in the t(8,21) is associated with the French-American-British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the general population and has been described in Down patients with AML-M2. Recently, a new rearrangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid transcript, has been described by molecular analysis as the most recurrent genetic lesion in childhood acute lymphoblastic leukemia (ALL). In order to investigate whether the t(12;21) could give a molecular clue as to the precise basis of the etiologic association between DS and acute lymphoblastic leukemia, we tested a series of 11 consecutive cases of ALL in DS children for the presence of the TEL/AML1 transcript, by RT-PCR analysis. We report absence of the TEL/AML1 rearrangement among the 11 cases tested. This data may be suggestive of alternative pathways involved in the pathogenesis of ALL in children with constitutional trisomy 21.

Adolescent↗

PubMed1997

Genetic heterogeneity of AIDS-related small non-cleaved cell lymphoma.

AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL) includes Burkitt's lymphoma (BL) and high-grade B-cell Burkitt-like lymphoma (BLL). Due to the marked polymorphism of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL), the morphologic distinction between these two types of lymphomas is frequently controversial, although it may bear clinical relevance. Although the molecular features of AIDS-BL have been clarified to a certain extent, the genetic peculiarities of AIDS-BLL have not been investigated in detail. In this study we have compared morphologic and genetic features of AIDS-BL and AIDS-BLL in a blind coded fashion. Molecular studies were focused on the genetic lesions known to be implicated in AIDS-NHL, including alterations of c-MYC, BCL-6, p53, deletions of 6q, as well as infection by EBV and HHV-8. Alterations of c-MYC occurred in 10/10 AIDS-BL, whereas they were restricted to 2/10 AIDS-BLL (P < 0.01). Mutations of p53 were present in 5/10 AIDS-BL, whereas they were consistently absent among AIDS-BLL (n = 10; P < 0.05). Infection by EBV occurred in 30% of both AIDS-BL and AIDS-BLL. Rearrangements of BCL-6, deletions of 6q and infection by HHV-8 scored consistently negative in both AIDS-BL and AIDS-BLL. Based on the genetic lesions tested, the molecular profile of AIDS-BLL appears to be closer to that of AIDS-related diffuse large cell lymphoma (AIDS-DLCL) than to that of AIDS-BL. In contrast to AIDS-BLL however, AIDS-DLCL carried rearrangements of BCL-6 in a fraction of cases (2/9). This study, the largest of its kind reported so far, suggests that AIDS-BL and AIDS-BLL have a different molecular pathogenesis and that characterization of genetic lesions may help to distinguish between these two lymphomas.

Blotting, Southern↗

PubMed1997

Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic leukaemia.

The t(12;21)(p13;q22) translocation has been described recently as the most recurrent genetic lesion in paediatric acute lymphoblastic leukaemias (ALLs). It has also been associated with B-precursor lineage involvement and good outcome. We tested 51 diagnostic paediatric ALLs and found 11 cases with molecular evidence of the t(12;21). Interestingly, amongst t(12;21) positive patients, we report three cases with hybrid phenotype, and two cases showing an aggressive and fatal disease. Our data show that the t(12;21) does not represent an independent good-risk indicator. Long follow-ups and additional molecular investigations are needed to assess the prognostic and pathogenetic relevance of t(12;21) in childhood ALLs.

Cell Lineage↗

PubMed1997

Point mutations of the BCL-6 gene in Burkitt's lymphoma.

BCL-6 codes for a transcription factor implicated in chromosomal translocations of diffuse large cell lymphomas. Recent evidence indicates that BCL-6 may also be altered by mutations of its 5' non-coding regions. In this study we have investigated the distribution of BCL-6 5' mutations among 35 Burkitt's lymphoma cases representative of the epidemiologic variants of the disease. Mutations were detected in 6/21 (28.6%) sporadic Burkitt's lymphomas and 7/14 (50%) endemic Burkitt's lymphomas. These data expand the spectrum of B-cell non-Hodgkin's lymphomas associated with BCL-6 5' mutations and have implications for the pathogenesis, histogenesis and clinical monitoring of Burkitt's lymphoma.

Burkitt Lymphoma↗

PubMed1997

Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status.

In this study we investigated the presence of structural lesions in the ALL-1, p53 and p16 (cyclin-dependent kinase 4 inhibitor) genes in leukaemic cells obtained from 22 patients with infant acute leukaemia (aged < 18 months). Of these, 18 cases were classified as acute lymphoblastic leukaemia (ALL) and four as acute myeloid leukaemia (AML). Tumour DNAs were analysed by a combination of Southern blot. polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequence analyses. The results showed ALL-1 gene rearrangements in 15/22 (68%) cases, p53 gene mutations in 5/22 (26%), and a homozygous deletion of p16 in a single T-ALL case. p53 and p16 alterations were all found in the group of patients with ALL-1 gene rearrangements. p53 mutations were more often associated with a myeloid phenotype (3/5). In summary, multiple molecular alterations were found in 6/15 (40%) infant acute leukaemias with ALL-1 rearrangements. As to the clinical course, patients with additional lesions had similar clinical outcome with respect to patients with ALL-1 gene rearrangement as the sole genetic aberration. This may support the hypothesis that ALL-1 alterations are genetic events per se sufficient to confer a fully malignant phenotype to the leukaemic clone.

Acute Disease↗

PubMed1997

Analysis of human herpesvirus type 8 infection in AIDS-related and AIDS-unrelated primary central nervous system lymphoma.

Human herpesvirus type 8 (HHV-8) has been proposed as a pathogenetic factor for immunosuppression-associated primary central nervous system lymphoma (PCNSL). To verify this hypothesis, HHV-8 infection was investigated in 31 persons with PCNSL (16 AIDS-related, 15 AIDS-unrelated) and in 30 persons with systemic B cell non-Hodgkin's lymphomas (B-NHL; 15 AIDS-related, 15 AIDS-unrelated). All subjects with PCNSL scored negative by single-step polymerase chain reaction (PCR), suggesting a tumor virus load of <100 viral copies/200,000 human haploid genome equivalents (HHGE). By applying Poisson assumptions to nested PCR, 16 of 31 persons with PCNSL were devoid of HHV-8 sequences: 1 subject with AIDS and PCNSL had 1-100 viral copies/200,000 HHGE, and 14 with PCNSL had <1 viral copy/200,000 HHGE. Similarly, 10 of 30 persons with systemic B-NHL were devoid of HHV-8 sequences; 20 had <1 viral copy/200,000 HHGE. The extremely low levels of infection rule out a role of HHV-8 in PCNSL pathogenesis and are consistent with HHV-8 infection of bystander cells contaminating the tumor clone.

AIDS-Related Opportunistic Infections↗