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  1. Article: Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia.

    Vonk, Christian M / Al Hinai, Adil S A / Hanekamp, Diana / Valk, Peter J M

    Cancers

    2021  Volume 13, Issue 21

    Abstract: Initial induction chemotherapy to eradicate the bulk of acute myeloid leukemia (AML) cells results in complete remission (CR) in the majority of patients. However, leukemic cells persisting in the bone marrow below the morphologic threshold remain ... ...

    Abstract Initial induction chemotherapy to eradicate the bulk of acute myeloid leukemia (AML) cells results in complete remission (CR) in the majority of patients. However, leukemic cells persisting in the bone marrow below the morphologic threshold remain unaffected and have the potential to proliferate and re-emerge as AML relapse. Detection of minimal/measurable residual disease (MRD) is a promising prognostic marker for AML relapse as it can assess an individual patients' risk profile and evaluate their response to treatment. With the emergence of molecular techniques, such as next generation sequencing (NGS), a more sensitive assessment of molecular MRD markers is available. In recent years, the detection of MRD by molecular assays and its association with AML relapse and survival has been explored and verified in multiple studies. Although most studies show that the presence of MRD leads to a worse clinical outcome, molecular-based methods face several challenges including limited sensitivity/specificity, and a difficult distinction between mutations that are representative of AML rather than clonal hematopoiesis. This review describes the studies that have been performed using molecular-based assays for MRD detection in the context of other MRD detection approaches in AML, and discusses limitations, challenges and opportunities.
    Language English
    Publishing date 2021-10-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13215431
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: PPM1D mutations appear in complete remission after exposure to chemotherapy without predicting emerging AML relapse.

    Al Hinai, Adil S A / Grob, Tim / Rijken, Melissa / Kavelaars, François G / Zeilemaker, Annelieke / Erpelinck-Verschueren, Claudia A J / Sanders, Mathijs A / Löwenberg, Bob / Jongen-Lavrencic, Mojca / Valk, Peter J M

    Leukemia

    2021  Volume 35, Issue 9, Page(s) 2693–2697

    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Follow-Up Studies ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Protein Phosphatase 2C/genetics ; Remission Induction
    Chemical Substances PPM1D protein, human (EC 3.1.3.16) ; Protein Phosphatase 2C (EC 3.1.3.16)
    Language English
    Publishing date 2021-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-021-01155-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2295: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Archived bone marrow smears are an excellent source for NGS-based mutation detection in acute myeloid leukemia.

    Al Hinai, Adil S A / Grob, Tim / Kavelaars, François G / Rijken, Melissa / Zeilemaker, Annelieke / Erpelinck-Verschueren, Claudia A J / Gussinklo, Kirsten J / Sanders, Mathijs A / van Lom, Kirsten / Valk, Peter J M

    Leukemia

    2020  Volume 34, Issue 8, Page(s) 2220–2224

    MeSH term(s) Bone Marrow/pathology ; Calreticulin/genetics ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA Methyltransferase 3A ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Janus Kinase 2/genetics ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Mutation
    Chemical Substances CALR protein, human ; Calreticulin ; DNMT3A protein, human ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; DNA Methyltransferase 3A (EC 2.1.1.37) ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
    Language English
    Publishing date 2020-02-14
    Publishing country England
    Document type Letter
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-020-0744-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2295: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Grob, Tim / Al Hinai, Adil S A / Sanders, Mathijs A / Kavelaars, François G / Rijken, Melissa / Gradowska, Patrycja L / Biemond, Bart J / Breems, Dimitri A / Maertens, Johan / van Marwijk Kooy, Marinus / Pabst, Thomas / de Weerdt, Okke / Ossenkoppele, Gert J / van de Loosdrecht, Arjan A / Huls, Gerwin A / Cornelissen, Jan J / Beverloo, H Berna / Löwenberg, Bob / Jongen-Lavrencic, Mojca /
    Valk, Peter J M

    Blood

    2022  Volume 139, Issue 15, Page(s) 2347–2354

    Abstract: Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular ...

    Abstract Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular analysis of mutant TP53 AML and MDS-EB to dissect the molecular characteristics in detail and determine its impact on survival. We performed next-generation sequencing on 2200 AML/MDS-EB specimens and assessed the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease and studied the associations of these characteristics with overall survival. TP53 mutations were detected in 230 (10.5%) patients with AML/MDS-EB with a median variant allele frequency of 47%. Bi-allelic mutant TP53 status was observed in 174 (76%) patients. Multiple TP53 mutations were found in 49 (21%) patients. Concurrent mutations were detected in 113 (49%) patients. No significant difference in any of the aforementioned molecular characteristics of mutant TP53 was detected between AML and MDS-EB. Patients with mutant TP53 have a poor outcome (2-year overall survival, 12.8%); however, no survival difference between AML and MDS-EB was observed. Importantly, none of the molecular characteristics were significantly associated with survival in mutant TP53 AML/MDS-EB. In most patients, TP53 mutations remained detectable in complete remission by deep sequencing (73%). Detection of residual mutant TP53 was not associated with survival. Mutant TP53 AML and MDS-EB do not differ with respect to molecular characteristics and survival. Therefore, mutant TP53 AML/MDS-EB should be considered a distinct molecular disease entity.
    MeSH term(s) Cytogenetics ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Mutation ; Myelodysplastic Syndromes/diagnosis ; Tumor Suppressor Protein p53/genetics
    Chemical Substances TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2022-02-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021014472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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  5. Article ; Online: RNA sequencing reveals a unique fusion of the lysine (K)-specific methyltransferase 2A and smooth muscle myosin heavy chain 11 in myelodysplastic syndrome and acute myeloid leukemia.

    Sanders, Mathijs A / Kavelaars, François G / Zeilemaker, Annelieke / Al Hinai, Adil S A / Abbas, Saman / Beverloo, H Berna / van Lom, Kirsten / Valk, Peter J M

    Haematologica

    2014  Volume 100, Issue 1, Page(s) e1–3

    MeSH term(s) Aged ; Follow-Up Studies ; Gene Fusion ; High-Throughput Nucleotide Sequencing/methods ; Histone-Lysine N-Methyltransferase/genetics ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Myelodysplastic Syndromes/therapy ; Myeloid-Lymphoid Leukemia Protein/genetics ; Myosin Heavy Chains/genetics ; Oncogene Proteins, Fusion/genetics ; Prognosis ; Sequence Analysis, RNA/methods
    Chemical Substances KMT2A protein, human ; MYH11 protein, human ; Oncogene Proteins, Fusion ; Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; Myosin Heavy Chains (EC 3.6.4.1)
    Language English
    Publishing date 2014-12-29
    Publishing country Italy
    Document type Case Reports ; Letter
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2014.110775
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.76: Show issues Location:
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