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  • Beverloo, H. Berna  (2)
  • 2005-2009  (2)
  • 1
    Online Resource
    Online Resource
    CALM-AF10 and HOX11L2 Abnormalities Define Poor Prognostic Subgroups in Pediatric T-Cell Acute Lymphoblastic Leukemia.
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 3279-3279
    Details
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 3279-3279
    Abstract: Recognition of specific T-ALL subgroups based upon cytogenetic aberrations may have prognostic relevance. The prognostic relevance of recurrent molecular-cytogenetic abnormalities using RQ-PCR and FISH was established for T-ALL patients enrolled on the DCOG protocols, and assigned to SIL-TAL, HOX11, HOX11L2, or CALM-AF10 subgroups or a rest group lacking any of these abnormalities. RQ-PCR data almost completely matched with FISH data. CALM-AF10 was associated with a poor outcome (p=0.005), whereas HOX11L2 and TAL1 subgroups demonstrated a strong trend towards poor and good outcome, respectively. A significant association between HOX11L2 and poor outcome was validated in a second T-ALL cohort comprising 53 pediatric patients that were enrolled on the COALL97 protocol (p=0.01). The TAL1 subgroup was committed to αβ-lineage T-cell developmental stage. HOX11 T-ALLs were all CD1 positive without expression of Cytβ and/or TCR expression reflecting an early cortical developmental stage. The immunophenotype of the HOX11L2 subgroup was rather heterogeneous consisting of samples with TCRγδ expression as well as phenotypic immature cases. Only 41% of HOX11L2 positive cases expressed CD1, indicating that HOX11L2 and HOX11 represent different T-cell developmental stages. CALM-AF10 was associated with a very immature immunophenotype, frequently expressing CD34 and myeloid markers. The TAL1 subgroup was characterized by high expression levels of TAL1, but about half of the samples with no or other aberrations also highly expressed TAL1. LYL1 was highly expressed in the other subgroups, with the highest expression levels in the most immature subgroups. LMO2 gene expression levels closely matched with LYL1 levels. In conclusion, the presence of CALM-AF10 and HOX11L2 abnormalities define poor prognostic subgroups in pediatric T-ALL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V106.11.3279.3279
    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
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  • 2
    Online Resource
    Online Resource
    Prognostic Significance of Molecular-Cytogenetic Abnormalities in Pediatric T-ALL Is Not Explained by Immunophenotypic Differences.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4220-4220
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4220-4220
    Abstract: Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is characterized by recurrent chromosomal rearrangements that may have prognostic significance. T-ALL cases with specific aberrations may arrest at specific T-cell development stages. Two classification systems were developed to classify T-ALL into developmental subgroups, i.e. the European Group for the Immunological Characterization of Leukemias (EGIL) and the T-cell receptor (TCR) classification system. In this study, we investigated the relationship between molecular-cytogenetic abnormalities and T-cell development stage. We investigated whether arrest at specific T-cell stages explains the prognostic significance of molecular-cytogenetic abnormalities. To this aim, we extensively studied 72 pediatric T-ALL cases by FISH and RQ-PCR for the presence of genetic abnormalities and expression of transcription factors, by PCR and sequencing for NOTCH1 mutations and by flow-cytometry to determine the T-cell receptor status as well as CD marker expression. The median clinical follow-up was 5 years. HOX11 rearranged cases were CD1 positive consistent with a cortical stage, but as 4 out of 5 cases lacked cytoplasmatic-beta expression, developmental arrest may precede beta-selection. HOX11L2 was especially confined to immature and pre-AB developmental stages, but 3 out of 17 HOX11L2 mature cases were restricted to the γδ-lineage. TAL1 rearrangements were restricted to the αβ-lineage with most cases being TCRαβ positive. NOTCH1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage. The CALM-AF10 translocation as detected in 3 T-ALL patients was significantly associated with early relapse. TAL1 or HOX11L2 rearrangements were associated with trends to good and poor outcome, respectively. Cases with high TAL1 expression levels also demonstrated a trend towards good outcome, whereas cases with the lowest TAL1 levels had a poor outcome and were mostly HOX11L2 or CALM-AF10 positive. NOTCH1 mutations did not predict for poor outcome. Classification into T-cell developmental subgroups did not predict for outcome. In conclusion, the present study shows that differences in outcome for various molecular-cytogenetic subgroups cannot be attributed to differences in T-cell maturation stage.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.4220.4220
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    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
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