PMC7645062_01
Results of morphological and mutational analysis at diagnosis as well as clinical data of the patient. (A) Results of morphological analysis, which revealed a hyper-cellular bone marrow (Wright-Giemsa, x 1000). (B) Results of iron stain on BM samples, which showed ring sideroblasts (red arrow, x 1000). (C) Results of BM core biopsy, which showed pleomorphic megakaryocytes (HE, x 400). (D-F) Mutations of JAK2, SF3B1 and TP53 were detected by next-generation sequencing, respectively.
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The bone marrow (BM) aspirate was hypercellular, with myeloid versus erythroid ratio equals to 2.70. 0.5% of blasts and 8% of ring sideroblasts (RS) were detected in the BM (Fig. 1A and B), with no signs of dysplastic in granulocytic and megakaryocytic lineages. The megakaryocytes frequently formed dense clusters, adjacent to the bone marrow vascular sinuses and bone trabeculae, which are different from that in essential thrombocythemia (Fig. 1C). Next-generation sequencing (NGS) using a targeted 51-gene panel on BM samples revealed somatic mutations including JAK2 V617F (variant allele frequency, VAF, 90.3%), SF3B1 K666N (VAF,40.5%), and TP53 R181H (VAF,3.9%) (Fig. 1D-F). Hb gradually decreased to the upper limit of normal value. However, enlarged spleen (64 mm below the left costal margin at the midclavicular line, supplementary figure 1) and elevated LDH were detected at the 7-months follow-up, which implied disease progression.
Sequence data for SF3B1 and TP53. Sanger sequencing revealed SF3B1 K666N (A) but no mutations of TP53 (B). Clinical data of the patient (C). WBC: white blood cell, Hb: heamoglobin. Depicts the maximum length of change in spleen during therapy (D).
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Sanger sequencing revealed SF3B1K666N but no mutations of TP53 (Fig. 2A and B). Four months later, in October 2019, the spleen shrunk to 22 mm below the left costal margin at the midclavicular line and the Hb level decreased to 13.6 g/dL (Fig. 2C and D).