Secondary CNL after SAA reveals insights in leukemic transformation of bone marrow failure syndromes.


Journal

Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425

Informations de publication

Date de publication:
10 11 2020
Historique:
received: 22 01 2020
accepted: 14 10 2020
entrez: 9 11 2020
pubmed: 10 11 2020
medline: 15 5 2021
Statut: ppublish

Résumé

Acquired aplastic anemia and severe congenital neutropenia (SCN) are bone marrow (BM) failure syndromes of different origin, however, they share a common risk for secondary leukemic transformation. Here, we present a patient with severe aplastic anemia (SAA) evolving to secondary chronic neutrophilic leukemia (CNL; SAA-CNL). We show that SAA-CNL shares multiple somatic driver mutations in CSF3R, RUNX1, and EZH2/SUZ12 with cases of SCN that transformed to myelodysplastic syndrome or acute myeloid leukemia (AML). This molecular connection between SAA-CNL and SCN progressing to AML (SCN-AML) prompted us to perform a comparative transcriptome analysis on nonleukemic CD34high hematopoietic stem and progenitor cells, which showed transcriptional profiles that resemble indicative of interferon-driven proinflammatory responses. These findings provide further insights in the mechanisms underlying leukemic transformation in BM failure syndromes.

Identifiants

pubmed: 33166403
pii: S2473-9529(20)31949-2
doi: 10.1182/bloodadvances.2020001541
pmc: PMC7656927
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5540-5546

Informations de copyright

© 2020 by The American Society of Hematology.

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Auteurs

Laurent Schmied (L)

Division of Hematology and.
Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.

Patricia A Olofsen (PA)

Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Pontus Lundberg (P)

Division of Hematology and.

Alexandar Tzankov (A)

Division of Pathology, University Hospital Basel, Basel, Switzerland; and.

Martina Kleber (M)

Division of Hematology and.
Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.

Jörg Halter (J)

Division of Hematology and.

Mario Uhr (M)

Division of Hematology, Moncucco Hospital Lugano, Lugano, Switzerland.

Peter J M Valk (PJM)

Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Ivo P Touw (IP)

Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Jakob Passweg (J)

Division of Hematology and.

Beatrice Drexler (B)

Division of Hematology and.

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