GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Society of Hematology  (3)
  • Saglio, Giuseppe  (3)
  • 1
    Online Resource
    Online Resource
    Molecular response to imatinib in late chronic-phase chronic myeloid leukemia
    American Society of Hematology ; 2004
    In:  Blood Vol. 103, No. 6 ( 2004-03-15), p. 2284-2290
    Details
    In: Blood, American Society of Hematology, Vol. 103, No. 6 ( 2004-03-15), p. 2284-2290
    Abstract: Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191 patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously treated with interferon α. MR was assessed with real-time quantitative (TaqMan) reverse transcription–polymerase chain reaction and was expressed as the ratio between BCR/ABL and β2-microglobulin × 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85 patients. A reduction of the transcript level of more than 2 logs was achieved in all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months, with the transcript level undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by time. Only 1 of 22 negative cases has had a relapse as yet.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2003-07-2575
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Prediction of Response to Imatinib by Prospective Quantitation of BCR-ABL Transcript in Late Chronic Phase Chronic Myeloid Leukemia PatientsBy GIMEMA Working Party on CML.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 4672-4672
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4672-4672
    Abstract: Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for bcr-abl transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 3, 6 and 12 months or at the end of study treatment (12 months) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of Bcr-Abl transcript was expressed as the ratio of Bcr-Abl to β2-microglobulin (β2M). We show that, following initiation of imatinib, the early Bcr-Abl level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome after 6 and 12 months of treatment, and that these early trends were also predictive of progression-free survival.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.4672.4672
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Quantitative Detection of NPM1 Mutations as Marker of Minimal Residual Disease (MRD) in the Large Majority of AML with Normal Karyotype.
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 225-225
    Details
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 225-225
    Abstract: Normal cytogenetics in AML is a major drawback to detect minimal residual disease. We have identified heterozygous NPM1 mutations as the most frequent genetic lesion in AML with normal karyotype (NEJM2005:352,254). Mutations A, B and D, all characterized by tetranucleotide insertions, account for more than 90% of all mutations. NPM1 mutations are new important prognostic markers in AML with normal cytogenetics, being predictive of successful response to induction treatment (NEJM2005:352,254) and longer overall survival in cases without FLT3 mutations (Dohner K et al, and Schnittger S et al, Blood 2005, on line). Their clinical impact prompted us to develop a Real Time Quantitative PCR assay for the identification and monitoring of NPM1 mutants. Tests were set up using either cDNA (13 adult cases with mutation A and 1 with mutation B) or genomic DNA (gDNA) (7 pediatric and 8 adult patients). cDNA RQ-PCR . Forward primer was designed in exon 11, probe in exon 11/exon 12 junction (5′-FAM-3′-MGB) and reverse primers in exon 12. Samples were analyzed in ABI PRISM 7700 Sequence Detection System (Applied Biosystems). ABL1 gene was used as control. For the absolute quantitative assessment of NPM1 mutation A copies a standard curve with serial dilutions of a plasmid containing the target sequences was used. The highest reproducible sensitivity of this RQ-PCR assay was 10 molecules. The highest reproducible sensitivity of the relative quantification RQ-PCR assay for mutation A and B was 10−4. Thirteen AML NPM mutation A patients were monitored at diagnosis and over follow up. The number of mutated copies was high in all cases at diagnosis and significantly decreased after induction treatment in all cases with complete hematological remission. Only a slight decrease was observed in the case who did not reach remission. Patients with a complete hematological remission but MRD decrease 〈 3log showed a higher risk of relapse. gDNA RQ-PCR . specific forward primers for six different mutations were designed using Primer Express software to anneal to the mutated region of NPM exon 12. Reverse primers were designed on NPM1 exon 12. The TaqMan core reagent kit (Applied Biosystems) was used for RQ-PCR. The albumin gene was used as control. A reproducible sensitivity of 10−4 was reached in all but one case. The mean Ct of undiluted DNA samples was 23.3 (range 22.1–24.8). The mean slope of the dilution curves was 3.6 (2.9–4.0). High correlation coefficients (0.99 in all but one) were obtained. Using both cDNA and gDNA we set up sensitive and reproducible systems to detect minimal residual disease in 60% of AML with normal karyotype and NPM gene mutations. While gDNA RQ-PCR has the advantage to be directly related to the number of residual leukemic cells, cDNA RQ-PCR can be easily applied in samples collected in the routine diagnostic testing for common translocations. Large prospective studies are necessary to clarify the clinical impact of NPM1-based MRD monitoring of AML with normal karyotype.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V106.11.225.225
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...