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.

dx.doi.org/10.1182/bloodadvances.2020001541, hdl.handle.net/1765/132230
Blood Advances
Department of Hematology

Schmied, L. (Laurent), Olofsen, P.A. (Patricia A.), Lundberg, P. (Pontus), Tzankov, A, Kleber, M, Halter, J.P, … Drexler, B. (Beatrice). (2020). Secondary CNL after SAA reveals insights in leukemic transformation of bone marrow failure syndromes. Blood Advances, 4(21), 5540–5546. doi:10.1182/bloodadvances.2020001541