Cellular origin of prognostic chromosomal aberrations in AML patients

Research output: Contribution to journalJournal article – Annual report year: 2015Researchpeer-review

DOI

  • Author: Mora-Jensen, Helena

    Copenhagen University Hospital, Denmark

  • Author: Jendholm, Johan

    Copenhagen University Hospital, Denmark

  • Author: Rapin, Nicolas

    Copenhagen University Hospital, Denmark

  • Author: Andersen, M. K.

    Copenhagen University Hospital

  • Author: Roug, A. S.

    Aarhus University Hospital, Denmark

  • Author: Bagger, F. O.

    Copenhagen University Hospital

  • Author: Bullinger, Lars

    Ulm University Hospital, Germany

  • Author: Winther, Ole

    Cognitive Systems, Department of Applied Mathematics and Computer Science , Technical University of Denmark, Richard Petersens Plads, 2800, Kgs. Lyngby, Denmark

  • Author: Borregaard, N.

    Copenhagen University Hospital, Denmark

  • Author: Porse, Bo T.

    Copenhagen University Hospital, Denmark

  • Author: Theilgaard-Mönch, Kim

    Lund University, Sweden

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Acute myeloid leukemia (AML) represents an aggressive cancer entity, whose malignant cells respond abnormally to regulatory stimuli and have lost the ability to differentiate and become fully mature blood cells.1, 2 AML evolves through accumulation of independent genetic aberrations, including chromosomal structural rearrangements and single nucleotide variants (SNVs). Conventional AML diagnostics and recent seminal next-generation sequencing (NGS) studies have identified more than 200 recurrent genetic aberrations presenting in various combinations in individual patients. Significantly, many of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal karyotype have demonstrated the presence of prognostic driver aberrations (that is, NPM1, FLT3-ITD and FLT3-TKD) in committed HPCs but not in multipotent HSCs. However, the HSC populations lacking the prognostic driver aberrations contained preleukemic clones harboring a series of recurrent molecular aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs responded poorly to in vivo chemotherapy treatment as compared with t(9;11) AML originating from HPCs.
Original languageEnglish
JournalLeukemia
Volume29
Issue number8
Pages (from-to)1785-1789
ISSN0887-6924
DOIs
Publication statusPublished - 2015
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • ONCOLOGY, HEMATOLOGY, ACUTE MYELOID-LEUKEMIA, IDENTIFICATION, MUTATIONS, EVOLUTION, CANCER, CELLS

ID: 117348597