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Vincenzo Rossi

Publications and source records attributed to Vincenzo Rossi.

15 recordsLinked to original sources
PubMed2006

Monitoring of minimal residual disease in leukemia, advantages and pitfalls.

The term 'minimal residual disease' (MRD) defines the level of disease detectable in patients in clinical remission during therapy, below the detection limit of conventional methods. Very sensitive methods can be used, able to identify one leukemic cell out of 10,000 normal lymphocytes. In vivo measurements of leukemia cytoreduction reflect the combined effect of clinical and biological variables, thus providing direct information on the effectiveness of treatment in each patient. Thus, these methods can potentially be used for tailoring treatment and personalize the cure. Although MRD studies are becoming an integral part of the modern management of patients with leukemia, several parameters are critical for the application and interpretation of MRD studies, including therapeutic context, timing of sampling, target genes and sensitivity of the polymerase chain reaction (PCR) assay, inter-laboratory standardization (particularly relevant in multicenter studies), selection of patients, retrospective or prospective nature of the study. Methodologies and pitfalls as well as results of clinical uses of MRD will be reviewed in this article by selecting significant examples of its clinical impact in the management of patients with leukemia.

Flow Cytometry↗
PubMed2006

Diagnosis and monitoring of PML-RARA-positive acute promyelocytic leukemia by qualitative RT-PCR.

The t(15;17) is the diagnostic hallmark of acute promyelocytic leukemia (APL). As a result, the RARA and the promyelocytic leukemia (PML) genes are fused. The use of reverse-transcription polymerase chain reaction (RT-PCR) for the detection of the PML-RARA and RARA-PML fusion genes is the only technique that defines the PML breakpoint type and that allows the definition of a correct strategy for subsequent minimal residual disease (MRD) monitoring. Standardized conditions for RT-PCR analysis of fusion transcripts from chromosome aberrations in acute leukemia, including APL, have recently been reported in the context of the Biomed-1 Concerted Action, and are described in detail in this chapter.

Chromosomes, Human, Pair 15↗
PubMed2005

Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.

Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

Adolescent↗
PubMed2005

A wide role for NOTCH1 signaling in acute leukemia.

NOTCH1 is involved in the pathogenesis of T-acute lymphoblastic leukemia (T-ALL) carrying the very rare translocation t(7;9)(q34;q34.3). We analyzed the expression of genes belonging to NOTCH pathway, in acute leukemia primary samples and lymphoblastoid cell lines. NOTCH1 pathway activation represents a common feature of T-ALL when compared to acute myelogenous leukemia (AML) and B-cell precursor acute lymphoblastic leukemia. The contemporary expression of NOTCH1 and its ligands on cell surface contributes to high levels of pathway activity. AML primary samples show high levels of JAGGED1 expression despite the low NOTCH1 pathway activation, consistent with an autonomous JAGGED1 signaling in myeloid leukemogenesis.

Burkitt Lymphoma↗
PubMed2004

Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease.

Platelets release glutamate upon activation and are an important clearance system of the amino acid from blood, through high-affinity glutamate uptake, similar to that described in brain synaptosomes. Since platelet glutamate uptake is decreased in neurodegenerative disorders, we performed a morphological and molecular characterization of platelet glutamate transporters. The three major brain glutamate transporters EAAT1, EAAT2 and EAAT3 are expressed in platelets, with similar molecular weight, although at lower density than brain. A Na(+)-dependent-high-affinity glutamate uptake was competitively inhibited by known inhibitors but not by dihydrokainic acid, suggesting platelet EAAT2 does not play a major role in glutamate uptake at physiological conditions. We observed decreased glutamate uptake V(max), without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction compared to age-matched controls, which could explain the decrease of platelet uptake previously described. Platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neuropsychiatric disorders.

Aged↗
PubMed2004

WT1 gene expression: useful marker for minimal residual disease in childhood myelodysplastic syndromes and juvenile myelo-monocytic leukemia?

The WT1 gene is considered to be highly expressed in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia and is thought to play a key role in maintaining the viability of leukemia cells. However, little is known about the WT1 gene expression levels in pediatric patients with juvenile myelo-monocytic leukemia (JMML) and myelodysplastic syndromes (MDS). We studied WT1 expression in diagnostic bone marrow (BM) and peripheral blood (PB) samples of 90 patients with JMML, low grade MDS, advanced MDS and myelodysplasia-related AML in BM (n = 20) and PB (n = 18) samples of normal healthy volunteer donors.

Anemia, Refractory, with Excess of Blasts↗
PubMed2003

Expression profile and cellular localization of maize Rpd3-type histone deacetylases during plant development.

We analyzed the expression profile and cellular localization of the maize (Zea mays) Rpd3-type histone deacetylases genes ZmRpd3/101, ZmRpd3/102, and ZmRpd3/108 (indicated as ZmHDA101, ZmHDA102, and ZmHDA108 in the Plant Chromatin Database). This study shows that maize Rpd3 transcripts are present in all the organs and cellular domains analyzed, but we found that their amounts change during development, accumulating in the inner region of the endosperm, in vascular zones of the nucellus, in the tapetum, and in the tetrads. A similar expression profile and nucleus-cytoplasmic localization was observed for ZmRpd3 proteins. Glutathione S-transferase pull-down assays show that ZmRpd3 proteins can interact with the maize retinoblastoma-related (ZmRBR1) protein, an important regulator of cell cycle progression, and with the maize retinoblastoma-associated protein (ZmRbAp1). However, the three ZmRpd3 proteins do not mutually compete in the binding. These results suggest a general role of ZmRpd3 genes in the plant cell cycle and development. These observations also provide indications on possible mechanisms regulating their transcription and protein accumulation. Similarities in the gene expression profiles and protein interactions may indicate that functional redundancy among members of the ZmRpd3 gene family exists. However, a degree of functional divergence is also supported by our findings.

Amino Acid Sequence↗
PubMed2003

A maize histone deacetylase and retinoblastoma-related protein physically interact and cooperate in repressing gene transcription.

In mammalian cells the product of the human retinoblastoma tumour suppressor gene (pRb) can recruit Rpd3-like histone deacetylases to repress transcription. In this study, we investigated whether this mechanism might also be relevant in plants and found both conserved and distinct features. The expression profiles of the Zea mays Rpd3-type histone deacetylase (ZmRpd3I) and the retinoblastoma-related (ZmRBR1) homologues were analysed during endosperm development. GST pull-down and immunoprecipitation experiments showed a physical interaction between ZmRBRI and ZmRpd3I. Because ZmRpd3I lacks a LXCXE motif, conserved in several pRb-interacting proteins, we have mapped the amino acid domains involved in the ZmRBR1/ZmRpd3I interaction. Furthermore, we observed that ZmRbAp1, a maize member of the MSI/RbAp family, facilitated this protein interaction. Co-transformations of tobacco protoplasts with plasmids expressing ZmRBRI and ZmRpd3I showed that the two proteins cooperate in repressing gene transcription. Our findings represent the first indication that in plants a regulator of important biological processes, ZmRBRI, can recruit a histone deacetylase, ZmRpd3I, to control gene transcription.

Binding Sites↗
PubMed2003

FLT3 internal tandem duplication in childhood acute myeloid leukaemia: association with hyperleucocytosis in acute promyelocytic leukaemia.

We evaluated the incidence of FLT3/internal tandem duplication (ITD) mutation in childhood acute myeloid leukaemia (AML) diagnosed over 15 years. FLT3/ITD was found in 10 of 45 (22.2%) non-acute promyelocytic leukaemia (non-APL) patients. The 5-year event-free survival of non-APL patients was higher in FLT3/ITD-negative versus -positive patients (48.9%, SE 8.9, vs 20.0%, SE 16.1, P = 0.03). In childhood APL, FLT3/ITD incidence was higher than in non-APL, although not statistically significant (10 out of 29 patients, 34.5%, P = 0.29). In APL patients, FLT3/ITD was strongly correlated to a higher white blood cell count at diagnosis and the M3 French-American-British subtype.

Adolescent↗
PubMed2003

Regulation and processing of maize histone deacetylase Hda1 by limited proteolysis.

A maize histone deacetylase gene was identified as a homolog of yeast Hda1. The predicted protein corresponds to a previously purified maize deacetylase that is active as a protein monomer with a molecular weight of 48,000 and is expressed in all tissues of germinating embryos. Hda1 is synthesized as an enzymatically inactive protein with an apparent molecular weight of 84,000 that is processed to the active 48-kD form by proteolytic removal of the C-terminal part, presumably via a 65-kD intermediate. The enzymatically inactive 84-kD protein also is part of a 300-kD protein complex of unknown function. The proteolytic cleavage of ZmHda1 is regulated during maize embryo germination in vivo. Expression of the recombinant full-length protein and the 48-kD form confirmed that only the smaller enzyme form is active as a histone deacetylase. In line with this finding, we show that the 48-kD protein is able to repress transcription efficiently in a reporter gene assay, whereas the full-length protein, including the C-terminal part, lacks full repression activity. This report on the processing of Hda1-p84 to enzymatically active Hda1-p48 demonstrates that proteolytic cleavage is a mechanism to regulate the function of Rpd3/Hda1-type histone deacetylases.

Amino Acid Sequence↗
PubMed2003

Minimal residual disease as a surrogate marker for risk assignment to ALL patients.

The use of minimal residual disease (MRD) measurement as a "surrogate" marker of molecular response to treatment, can potentially improve the evaluation of treatment response and enable estimates of the residual leukemic cell burden during clinical remission, thereby improving the selection of therapeutic strategies and, possibly, long-term clinical outcome. The most specific and sensitive methods for MRD monitoring currently available are polymerase chain reaction amplification of fusion transcripts and rearranged immunoglobulin or antigen-receptor genes, and flow cytometric detection of aberrant immunophenotypes. Several retrospective studies in childhood acute lymphoid leukemias (ALL) have used one of the different approaches for the detection of MRD. The strong association between MRD and risk of relapse was observed in children and adult patients irrespective of the methodology used. The promising results on the predictivity of MRD evaluation at the end of induction treatment has challenged the need for a new definition of remission. There is now urgent need to incorporate MRD data in clinical studies, properly designed to address treatment questions. In this context, several ongoing cooperative study groups have adopted a MRD-based risk group classification to explore whether a better tailored treatment would result in further improvement in cure rates for children with ALL.

Biomarkers, Tumor↗
PubMed2002

Insights into the G1/S transition in plants.

The G1/S transition generally represents the principal point of commitment to cell division. Many of the components of the cell cycle core machinery regulating the G1/S transition in plants have been recently identified. Although plant regulators of the G1/S transition display structural and biochemical homologies with their animal counterparts, their functions in integrating environmental stimuli and the developmental program within cell cycle progression are often plant-specific. In this review, recent progress in understanding the role of plant G1/S transition regulators is presented. Emerging evidence concerning the mechanisms of G1/S control in response to factors triggering the cell cycle and the integration of these mechanisms with plant development is also discussed.

Cell Cycle↗
PubMed2002

Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

Adolescent↗
PubMed2002

Monitoring minimal residual disease using chromosomal translocations in childhood ALL.

Clonal chromosomal abnormalities have been identified in approximately 80% of childhood ALL. In most instances the genes disrupted by these abnormalities have been identified, thus providing important insights into disease pathogenesis and normal cellular physiology. Polymerase chain reaction (PCR) amplification of fusion transcripts resulting from chromosomal translocations has emerged as a sensitive and reproducible method to monitor minimal residual disease (MRD) in childhood ALL. The measure of the initial response to therapy in patients who have achieved complete remission by morphological standards can dissect clinical heterogeneity within the genetically homogeneous childhood ALL subgroup. Moreover, MRD monitoring can be applied to predict impending relapses early. Despite notable progress with this method, several critical issues must be resolved before MRD determinations can be routinely considered in clinical decision making. This chapter will focus on the main progress and common pitfalls in the PCR detection of chromosomal translocations applied to clinical studies.

Child↗