The transcription nuclear factor κ B (NF-κB) can intervene in oncogenesis through to its capacity... more The transcription nuclear factor κ B (NF-κB) can intervene in oncogenesis through to its capacity to regulate the expression of a large number of genes that regulate apop- tosis, cell proliferation and differentiation as well as inflammation, angiogenesis and tumor migration. Impaired NF-κB activity has been demonstrated not only in solid can- cers but also in various types of hematologic
The outcome for adult with Ph + leukemias (ALL and CML) has improved dra- matically with current ... more The outcome for adult with Ph + leukemias (ALL and CML) has improved dra- matically with current therapy including use of Tyrosine Kinase Inhibitors (TKIs), such as imatinib, nilotinib or dasatinib. The complete hematological remission is obtained in about 98% of early chronic phase CML patients treat- ed with TKIs. But the emergence of resistance to imatinib has become a
The Wilms tumor gene was identified as a tumor suppressor gene responsible for a particular type ... more The Wilms tumor gene was identified as a tumor suppressor gene responsible for a particular type of kidney tumor. Several years ago, it was demonstrated that it is also overexpressed in acute and chronic leukemias. Although the exact role of this gene in the hematopoietic system is still quite completely obscure, it represents a reliable marker for the detection of the presence of leukemic cells. WT1 quantitative assessment may therefore represent a useful tool for the diagnosis and follow up of leukemia patients. In this chapter, we describe the method for the quantification of WT1 transcript by real-time polymerase chain reaction.
Monitoring of acute leukemia patients during and after treatment for the presence of remaining le... more Monitoring of acute leukemia patients during and after treatment for the presence of remaining leukemic cells (minimal residual disease, MRD) has been shown to give major insight into the effectiveness of treatment. However, so far the applicability of this strategy has been limited to those leukemia subsets characterized by genetic markers amenable to sensitive detection by PCR. Although PCR for immunoglobulin and T cell receptor gene rearrangement represents the gold standard for MRD detection in most cases of ALL without any fusion gene transcripts as molecular markers available, the situation in AML is more complicated because, at present, more than 50% of them lack any sort of clonality markers suitable for MRD monitoring. Thus, a number of studies have been performed in an attempt to identify cytogenetic and molecular abnormalities associated with leukemic transformation. In this paper we describe the effectiveness of the quantitative assessment of the Wilms tumor gene (WT1) t...
The Wilms tumor suppressor gene (WT1) is overexpressed in a number of human hematological maligna... more The Wilms tumor suppressor gene (WT1) is overexpressed in a number of human hematological malignancies, including chronic myeloid leukemia (CML). Although at present, the biological significance of WT1 expression in CML in still unclear, this marker could represent a useful tool for molecular monitoring of CML patients prior to and post imatinib therapy. In fact, the use of real-time polymerase chaine reaction (PCR) to quantitatively measure the WT1 transcript amount may be a predictor of patient response to imatinib therapy.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 15, 2003
To determine whether pattern of WT1 gene expression is a useful marker for establishing prognosis... more To determine whether pattern of WT1 gene expression is a useful marker for establishing prognosis and tracking disease progression in patients with myelodysplastic syndromes (MDS). We performed a quantitative assessment of the WT1 transcript amount by real-time quantitative polymerase chain reaction (RQ-PCR) in 173 samples (131 bone marrow samples and 42 peripheral-blood samples) from 131 patients with MDS (79 patients with refractory anemia [RA], 31 with RA with excess blasts [RAEB], 18 with secondary acute myeloid leukemia [s-AML] evolved from MDS, and three with deletion of 5q as the sole cytogenetic abnormality). Values obtained were correlated with the blast percentage and International Prognostic Scoring System (IPSS) score. Sixty-five percent of BM and 78% of PB samples for RA and 100% of BM and PB samples of RAEB and s-AML expressed WT1 transcript amounts greater than the level observed in healthy volunteers. The degree of WT1 expression was highly correlated with the type o...
The Philadelphia chromosome (Ph-chromosome) has long represented the only cytogenetic abnormality... more The Philadelphia chromosome (Ph-chromosome) has long represented the only cytogenetic abnormality known to be associated with a specific malignant disease in humans, being present in more than 95% of patients with chronic myelogenous leukemia. This abnormality is the result of a reciprocal translocation between the long arms of chromosome 9 and 22, t(9;22)(q34;q11), and its presence is not restricted to chronic myelogenous leukemia, but can also be found in 30% of cases of acute lymphoblastic leukemia in adults. In the 1980s, the molecular counterpart of the chromosomal rearrangement was identified to consist of the juxtaposition of parts of the BCR and ABL genes to form a BCR-ABL hybrid gene. The resulting chimeric proteins (P210 and P190), which retain constitutively activated tyrosine kinase activity, have demonstrated a causative role in the genesis of the leukemic process. Although many aspects of the BCR-ABL driven transformation remain unsolved, great advances in understandin...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2009
Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteri... more Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteristics. It remains to be established whether relapse risk can be better predicted through assessment of minimal residual disease (MRD). One proposed marker is the Wilms tumor gene WT1, which is overexpressed in most patients with AML, thus providing a putative target for immunotherapy, although in the absence of a standardized assay, its utility for MRD monitoring remains controversial. Nine published and in-house real-time quantitative polymerase chain reaction WT1 assays were systematically evaluated within the European LeukemiaNet; the best-performing assay was applied to diagnostic AML samples (n = 620), follow-up samples from 129 patients treated with intensive combination chemotherapy, and 204 normal peripheral blood (PB) and bone marrow (BM) controls. Considering relative levels of expression detected in normal PB and BM, WT1 was sufficiently overexpressed to discriminate > or =...
The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial... more The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known.
The transcription nuclear factor κ B (NF-κB) can intervene in oncogenesis through to its capacity... more The transcription nuclear factor κ B (NF-κB) can intervene in oncogenesis through to its capacity to regulate the expression of a large number of genes that regulate apop- tosis, cell proliferation and differentiation as well as inflammation, angiogenesis and tumor migration. Impaired NF-κB activity has been demonstrated not only in solid can- cers but also in various types of hematologic
The outcome for adult with Ph + leukemias (ALL and CML) has improved dra- matically with current ... more The outcome for adult with Ph + leukemias (ALL and CML) has improved dra- matically with current therapy including use of Tyrosine Kinase Inhibitors (TKIs), such as imatinib, nilotinib or dasatinib. The complete hematological remission is obtained in about 98% of early chronic phase CML patients treat- ed with TKIs. But the emergence of resistance to imatinib has become a
The Wilms tumor gene was identified as a tumor suppressor gene responsible for a particular type ... more The Wilms tumor gene was identified as a tumor suppressor gene responsible for a particular type of kidney tumor. Several years ago, it was demonstrated that it is also overexpressed in acute and chronic leukemias. Although the exact role of this gene in the hematopoietic system is still quite completely obscure, it represents a reliable marker for the detection of the presence of leukemic cells. WT1 quantitative assessment may therefore represent a useful tool for the diagnosis and follow up of leukemia patients. In this chapter, we describe the method for the quantification of WT1 transcript by real-time polymerase chain reaction.
Monitoring of acute leukemia patients during and after treatment for the presence of remaining le... more Monitoring of acute leukemia patients during and after treatment for the presence of remaining leukemic cells (minimal residual disease, MRD) has been shown to give major insight into the effectiveness of treatment. However, so far the applicability of this strategy has been limited to those leukemia subsets characterized by genetic markers amenable to sensitive detection by PCR. Although PCR for immunoglobulin and T cell receptor gene rearrangement represents the gold standard for MRD detection in most cases of ALL without any fusion gene transcripts as molecular markers available, the situation in AML is more complicated because, at present, more than 50% of them lack any sort of clonality markers suitable for MRD monitoring. Thus, a number of studies have been performed in an attempt to identify cytogenetic and molecular abnormalities associated with leukemic transformation. In this paper we describe the effectiveness of the quantitative assessment of the Wilms tumor gene (WT1) t...
The Wilms tumor suppressor gene (WT1) is overexpressed in a number of human hematological maligna... more The Wilms tumor suppressor gene (WT1) is overexpressed in a number of human hematological malignancies, including chronic myeloid leukemia (CML). Although at present, the biological significance of WT1 expression in CML in still unclear, this marker could represent a useful tool for molecular monitoring of CML patients prior to and post imatinib therapy. In fact, the use of real-time polymerase chaine reaction (PCR) to quantitatively measure the WT1 transcript amount may be a predictor of patient response to imatinib therapy.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 15, 2003
To determine whether pattern of WT1 gene expression is a useful marker for establishing prognosis... more To determine whether pattern of WT1 gene expression is a useful marker for establishing prognosis and tracking disease progression in patients with myelodysplastic syndromes (MDS). We performed a quantitative assessment of the WT1 transcript amount by real-time quantitative polymerase chain reaction (RQ-PCR) in 173 samples (131 bone marrow samples and 42 peripheral-blood samples) from 131 patients with MDS (79 patients with refractory anemia [RA], 31 with RA with excess blasts [RAEB], 18 with secondary acute myeloid leukemia [s-AML] evolved from MDS, and three with deletion of 5q as the sole cytogenetic abnormality). Values obtained were correlated with the blast percentage and International Prognostic Scoring System (IPSS) score. Sixty-five percent of BM and 78% of PB samples for RA and 100% of BM and PB samples of RAEB and s-AML expressed WT1 transcript amounts greater than the level observed in healthy volunteers. The degree of WT1 expression was highly correlated with the type o...
The Philadelphia chromosome (Ph-chromosome) has long represented the only cytogenetic abnormality... more The Philadelphia chromosome (Ph-chromosome) has long represented the only cytogenetic abnormality known to be associated with a specific malignant disease in humans, being present in more than 95% of patients with chronic myelogenous leukemia. This abnormality is the result of a reciprocal translocation between the long arms of chromosome 9 and 22, t(9;22)(q34;q11), and its presence is not restricted to chronic myelogenous leukemia, but can also be found in 30% of cases of acute lymphoblastic leukemia in adults. In the 1980s, the molecular counterpart of the chromosomal rearrangement was identified to consist of the juxtaposition of parts of the BCR and ABL genes to form a BCR-ABL hybrid gene. The resulting chimeric proteins (P210 and P190), which retain constitutively activated tyrosine kinase activity, have demonstrated a causative role in the genesis of the leukemic process. Although many aspects of the BCR-ABL driven transformation remain unsolved, great advances in understandin...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2009
Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteri... more Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteristics. It remains to be established whether relapse risk can be better predicted through assessment of minimal residual disease (MRD). One proposed marker is the Wilms tumor gene WT1, which is overexpressed in most patients with AML, thus providing a putative target for immunotherapy, although in the absence of a standardized assay, its utility for MRD monitoring remains controversial. Nine published and in-house real-time quantitative polymerase chain reaction WT1 assays were systematically evaluated within the European LeukemiaNet; the best-performing assay was applied to diagnostic AML samples (n = 620), follow-up samples from 129 patients treated with intensive combination chemotherapy, and 204 normal peripheral blood (PB) and bone marrow (BM) controls. Considering relative levels of expression detected in normal PB and BM, WT1 was sufficiently overexpressed to discriminate > or =...
The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial... more The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known.
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Papers by Daniela Cilloni