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

ABSTRACT: 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.

SUBMITTER: Schmied L 

PROVIDER: S-EPMC7656927 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Schmied Laurent L   Olofsen Patricia A PA   Lundberg Pontus P   Tzankov Alexandar A   Kleber Martina M   Halter Jörg J   Uhr Mario M   Valk Peter J M PJM   Touw Ivo P IP   Passweg Jakob J   Drexler Beatrice B  

Blood advances 20201101 21

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  ...[more]

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