A 68-Year-Old Man with a Cytogenetic Diagnosis of Chronic Myeloid Leukemia and Bone Marrow Findings of Philadelphia Chromosome Translocation Between the Long Arm of Chromosomes 9 and 22, Leading to the BCR-ABL1 Fusion Gene and V617F Mutation in the JAK2 Gene

Patient: Male, 68-year-old Final Diagnosis: CML Symptoms: Leukocytosis • splenomegaly Clinical Procedure: Bone marrow biopsy Specialty: Hematology OBJECTIVE: Rare disease BACKGROUND: Breakpoint cluster region (BCR)-Abelson murine leukemia (ABL1) and Janus Kinase-2 (JAK2) mutations have been thought to be mutually exclusive in myeloproliferative neoplasms (MNPs), but recent data suggest that they can occur together. CASE REPORT: A 68-year-old man was referred to the hematology clinic because of an elevated white blood cell count. His medical history included type II diabetes mellitus, hypertension, and retinal hemorrhage. Fluorescence in situ hybridization analysis of the bone marrow was positive for BCR-ABL1 in 66/100 cells. Conventional cytogenetics was positive for the Philadelphia chromosome in 16/20 counted cells. The percentage of BCR-ABL1 was 12%. Considering the patient’s age and medical comorbidities, he was started on imatinib 400 mg once daily. Further tests showed JAK2 V617F mutation positivity and absence of acquired von Willebrand disease. He was then started on aspirin 81 mg and hydroxyurea 500 mg once daily, which was later increased to 1000 mg daily. The patient achieved a major molecular response after 6 months of treatment, with undetectable BCR-ABL1 levels. CONCLUSIONS: BCR-ABL1 and JAK2 mutations can co-existence in MNPs. Physicians must suspect the presence of one of the MPNs in chronic myeloid leukemia (CML) patients with persistent or increased thrombocytosis, an atypical course of the disease, or hematological abnormalities despite evidence of response or remission of CML. Therefore, testing for JAK2 should be performed accordingly. Combining cytoreductive therapy with tyrosine kinase inhibitors (TKIs) is a therapeutic option when both mutations are present, and TKI alone is not sufficient to control peripheral blood cell counts.