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Abstract
Although recent work has described the microbiome in solid tumors, microbial content in hematological malignancies is not well-characterized. Here we analyze existing deep DNA sequence data from the blood and bone marrow of 1870 patients with myeloid malignancies, along with healthy controls, for bacterial, fungal, and viral content. After strict quality filtering, we find evidence for dysbiosis in disease cases, and distinct microbial signatures among disease subtypes. We also find that microbial content is associated with host gene mutations and with myeloblast cell percentages. In patients with low-risk myelodysplastic syndrome, we provide evidence that Epstein-Barr virus status refines risk stratification into more precise categories than the current standard. Motivated by these observations, we construct machine-learning classifiers that can discriminate among disease subtypes based solely on bacterial content. Our study highlights the association between the circulating microbiome and patient outcome, and its relationship with disease subtype.
Circulating microbiome has been very little studied for blood malignancies. Here, the authors show specific microbiome signatures in the blood are associated with different types of myeloid malignancies and specific genetic mutations.
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1 Case Western Reserve University, Department of Genetics and Genome Sciences, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847)
2 Munich Leukemia Laboratory, Munich, Germany (GRID:grid.420057.4) (ISNI:0000 0004 7553 8497)
3 Cleveland Clinic Foundation, Department of Translational Hematology & Oncology Research, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725)
4 Centro de Investigación del Cáncer, Salamanca, Spain (GRID:grid.428472.f) (ISNI:0000 0004 1794 2467)
5 Case Western Reserve University, Department of Computer Science, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847)