GLORIA

GEOMAR Library Ocean Research Information Access

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
Filter
  • American Society of Hematology  (3)
Materialart
Verlag/Herausgeber
  • American Society of Hematology  (3)
Sprache
Erscheinungszeitraum
Fachgebiete(RVK)
  • 1
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3786-3786
    Kurzfassung: BACKGROUND B-lineage acute lymphoblastic leukemia (B-ALL) represents the most common subtype in ALL. Genomic sequence information has been lacking in adult B-ALL, whose outcome remains dismal, while a comparison between genomic abnormalities in adult and pediatric groups is useful to further decipher disease mechanisms. METHODS We used whole exome sequencing (WES), copy number variation and molecular cytogenetics to catalog somatic mutations in 95 B-ALL patients (43 adults and 52 children).WES was conducted with appropriate depths for paired genomic DNA from bone marrow mononuclear cells at diagnosis and their matched peripheral blood samples during complete remission (CR) or saliva samples. Targeted deep sequencing (TDS) was performed in a validation cohort of 179 adult and 199 pediatric B-ALLs. RESULTS Eighty-four recurrent gene mutations were revealed by WES. Integrative analysis identified the involvement of 9 functional categories of genes: key fusions (KFs), epigenetic modifiers (EMs), signaling molecules (SMs), transcription factors (TFs), tumor suppressors (TSs), actin binding/cytoskeletons (ABCs), ion binding proteins (IBPs), trans-membrane proteins (TPs) and the others. Mutually cooperative or exclusive relationships were revealed among some of these categories. Genomic landscapes suggested two distinct mechanisms involved in the leukemogenesis: one is mainly driven by KFs together with mutations of TFs and TSs; the other results from the abnormalities of TFs and TSs, in cooperation with mutations of EMs, SMs, ABCs and IBPs recapitulating the role of KFs. A panel of histone/DNA methylation modifiers (HMMs) were revealed to bear potential value of relatively favorable prognosis in both adult and childhood patients. CONCLUSIONS We described the genome-wide abnormality patterns in adult B-ALL patients in comparison with those of pediatric cases, contributing to the understanding of leukemogenesis and the identification of potential new prognostic markers. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2014
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4718-4718
    Kurzfassung: Abstract 4718 Cytogenetic-molecular signature plays an important role in diagnosis, treatment and prognosis evaluation in acute lymphoblastic leukemia (ALL). With examination of karyotype and gene rearrangement, we investigated retrospectively the cytogenetic characteristics in 1331 adults and children with primary acute lymphoblastic leukemia (ALL) diagnosed from November 1989 to July 2007. Cytogenetic and molecular genetic analysis was carried out successfully in 1030 (77.39%) of 1331 cases, abnormal clone was detected in 629 (61.07%) cases. The abnormalities of t(9;22)/BCR-ABL and/or t(4;11)/MLL-AF4 were presented more commonly in adults than in children (25.39% Vs 10.34%,P 〈 0.001; 4.69% Vs 1.68%,P=0.0067). On the contrary, hyperdiploid( 〉 50) was more frequently seen in children than in adults (13.18% Vs 4.30%,P 〈 0.001). In addition, t(8;14)/IGH-MYC,t(12;21)/TEL-AML1 and t(11;19)/MLL-ENL were only observed in pediatric ALL. Compared with data of western countries, t(9;22)/BCR-ABL involvement in Chinese ALL patients, either in adults or in children, was more common. Simultaneously, a lower frequency of t(12;21)/TEL-AML1 was found in Chinese pediatric ALL patients. Ik6, one of IKZF1 deletion isoforms, was detected in 72.29% of ALL patients with Ph chromosome using reverse transcription-PCR amplification. In T-ALL, the frequency of the expression of SIL-TAL,CALM-AF10,HOX11,HOX11L2 gene and the mutation of NOTCH1 gene was 12.38%,4.69%,25.49%,24.51% and 32.99%, respectively. The overall survival of the children was superior to that of the adults, which was the same as previous reports by many other groups. According to the prognosis of patients, these cytogenetic-molecular signatures could be further classified into three subgroups in adult and four subgroups in children. Patients with Ik6 deletion isoform of IKZF1 gene had a significantly worse prognosis than those with wild type isoform (P=0.009). In T-ALL, patients with NOTCH1 mutation were related with poor outcome (P=0.007). Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2009
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    In: Blood, American Society of Hematology, Vol. 118, No. 20 ( 2011-11-17), p. 5593-5603
    Kurzfassung: To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)–ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients 〈 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2011
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...