Dominik Nann, Tim-Colin Schade, Mathis Overkamp, Lejla Mahmutovic, Eyyub Bag, Stephan Forchhammer, Julia Slotta-Huspenina, Ludmila Boudova, Karl Sotlar, Leticia Quintanilla-Martinez, Irina Bonzheim, Falko Fend
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引用次数: 0
Abstract
Myeloid sarcoma (MS) is a mass-forming extramedullary manifestation of myeloid blasts, either in relation to an underlying acute myeloid leukemia (AML), another myeloid neoplasm (MN) or as a de novo occurrence. Data on the genetic profile of MS are sparse. In this study, 41 MS of 34 patients, including 7 de novo cases and 24 patients with antecedent or synchronous MN, were analyzed with targeted next-generation sequencing (NGS), RNA-based fusion detection, and gene expression profiling (GEP). In 10 patients, a MS developed after stem cell transplantation for MN. Additionally, 21 available pre-transplant bone marrow biopsies (BMB) from 20 patients and 6 post-transplant BMB from 6 patients were investigated. The most frequently mutated gene was TET2 (41%), followed by NPM1 (38%) and NRAS (35%). Overall, 74% of the cases exhibited mutations affecting the MAPK/ERK pathway. AML-type fusions were detected in seven MS patients, who were younger than those without fusions (median 49 versus 67 years). Nine of 13 patients with a MN and available pre-transplant BMB showed additional mutations restricted to the MS, including an additional NRAS mutation in 3/5 cases with AML. Five of seven of patients with pre-transplant BMB without evidence of a MN revealed clonal hematopoiesis (CH), mostly shared TET2 mutations. Comparative GEP between BM and MS revealed upregulation of the MAPK/ERK pathway in MS and of gene sets relevant for interaction with the microenvironment. In conclusion, MS is characterized by a high incidence of MAPK/ERK pathway mutations and activation, frequent clonal evolution, and association with CH in elderly patients without recurrent AML-type fusions.
期刊介绍:
The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies.
The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.