#00065178

A 1-year-old girl presented for evaluation of persistent thrombocytosis (range, 678 000-909 000/μL) with white blood cell (WBC) counts and hemoglobin within normal limits. No other peripheral blood abnormalities were noted. Bone marrow aspirate revealed progressive trilineage hematopoiesis (panel A; 40× objective), increased, hypersegmented megakaryocytes (panels B and C; 100× objective), and no increase in blasts or immunophenotypically abnormal population by flow cytometry. Bone marrow was normocellular (∼80%, clot section; panels D and E, 40× objective). No significant fibrosis was observed with reticulin stain (panel F; 40× objective). Cytogenetic studies showed a normal female karyotype (46,XX[20]), whereas next-generation sequencing (NGS) detected a JAK2 R564Q mutation at an allele frequency of 44.5%. The patient's mother was also found to have thrombocytosis and normal WBC counts and hemoglobin, and further evaluation of the mother’s bone marrow demonstrated findings similar to those seen in our patient: normocellular marrow with trilineage hematopoiesis, increased megakaryocytes, no immunophenotypically abnormal population, no reticulin fibrosis, normal female karyotype, and JAK2 R564Q mutation by NGS with allele frequency of 51%.

To our knowledge, this is the second report of familial thrombocytosis with germline JAK2 R564Q mutation and the first report of bone marrow findings. Experimental studies have shown that JAK2 R564Q causes similar levels of increased kinase activity but milder growth-promoting effects when compared with JAK2 V617F, which may explain the difference in clinical outcome.

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