The Missing LNK: Evolution from Cytosis to Chronic Myelomonocytic Leukemia in a Patient with Multiple Sclerosis and Germline SH2B3 Mutation

Figure 1

(a) Erythroid nuclear dyskinesis (bone marrow aspirate, 600x magnification Wright-Giemsa staining). (b) Megakaryocyte with unremarkable nuclear lobes (bone marrow aspirate smear, 500x magnification; Wright-Giemsa staining). (c) Hypercellular marrow with focal megakaryocyte clustering (core biopsy, 500x magnification; Hematoxylin and Eosin staining). (d) Hypersegmented neutrophil (peripheral blood, 600x magnification; Hematoxylin and Eosin staining). (e) Hypercellular marrow with micro-megakaryocyte (core biopsy, 1000x magnification, Hematoxylin and Eosin staining). (f) The SH2B3 p.E395K; c 1183G > A mutation identified by NGS as shown in the Integrative Genomics Viewer (IGV) (Broad Institute, Cambridge MA). The blue and red bars represent reverse and forward reads, respectively, and the bars with green As are mutated reads. This image demonstrates the mutation from DNA extracted from the follow-up bone marrow specimen. (g) The SH2B3 c.1183G > A (p.E395K) heterozygous missense variant detected in the targeted sequencing study (RefSeq NM_005475.2) by direct sequence analysis utilizing automated fluorescence dideoxy sequencing. The red arrow and box demonstrate the missense variant region observed in the genomic DNA extracted from the cultured skin fibroblasts.