Case report of a patient with chronic myeloid leukemia, BCR::ABL1 positive presented with isolated thrombocytosis and an uncommon JAK2 alteration detected in peripheral blood

Chronic myeloid leukemia (CML) is a common myeloproliferative neoplasm (MPN). However, CML presenting with isolated thrombocytosis and lacking all the typical features of CML is quite rare. The purpose of this report is to demonstrate the importance of BCR::ABL1 testing for correct diagnosis and treatment even when the presenting features are unusual for CML. We report a case of isolated thrombocytosis with subsequently discovered alternative splicing of JAK2 resulting in skipping of exon 15 in the peripheral blood as the initial presentation of CML in a 67-year-old male with metastatic hepatocellular carcinoma, with BCR::ABL1 detected in the bone marrow aspirate. Bone marrow aspirate was collected in EDTA for evaluation and testing. Bone marrow clot and core sections were obtained and the core was decalcified, then each was fixed in neutral-buffered formalin (10%). The clot and core were embedded in formalin and sectioned at 4 microns for evaluation. Bone marrow aspirate and biopsy demonstrated markedly increased megakaryocytes with clustering. The chromosome analysis demonstrated t(9;22) and molecular studies for BCR::ABL1 were positive. JAK2 , MPL , and CALR mutations were negative. The patient did not show a response to hydroxyurea (HU) as the initial treatment. His platelet count normalized within 1 month after treatment with Tyrosine kinase inhibitor (TKI) Imatinib. This report highlights the importance of pursuing BCR::ABL1 testing in the workup of patients with isolated thrombocytosis, even in the presence of abnormal JAK2 transcripts and unusual bone marrow features.