1. Secondary CNL after SAA reveals insights in leukemic transformation of bone marrow failure syndromes
- Author
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Alexandar Tzankov, Pontus Lundberg, Martina Kleber, Jakob Passweg, Mario Uhr, Joerg Halter, Ivo P. Touw, Laurent Schmied, Beatrice Drexler, Patricia A. Olofsen, Peter J. M. Valk, and Hematology
- Subjects
Neutropenia ,Clinical Trials and Observations ,Chronic neutrophilic leukemia ,Transcriptome ,chemistry.chemical_compound ,hemic and lymphatic diseases ,medicine ,Congenital Bone Marrow Failure Syndromes ,Humans ,Progenitor cell ,Congenital Neutropenia ,business.industry ,Anemia, Aplastic ,Myeloid leukemia ,Hematology ,medicine.disease ,Leukemia, Myeloid, Acute ,Haematopoiesis ,medicine.anatomical_structure ,nervous system ,RUNX1 ,chemistry ,Mutation ,Cancer research ,Bone marrow ,business - 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.
- Published
- 2020