Burkitt leukemia with precursor B-cell features that developed after ruxolitinib treatment in a patient with hydroxyurea-refractory JAK2 V617F -myeloproliferative neoplasm.

A 62-year-old woman, who had a 16-year history of JAK2 ^V617F -mutated myeloproliferative neoplasm (MPN), developed Burkitt leukemia (BL) 16 months after treatment with ruxolitinib to control hydroxyurea-refractory conditions. BL cells were CD10 ⁺ , CD19 ⁺ , CD20 ^- , CD34 ^- , cytoplasmic CD79a ⁺ , and TdT ⁺ , and lacked surface immunoglobulins but expressed the cytoplasmic μ heavy chain. In the bone marrow, nuclear MYC ⁺ BL cells displaced the MPN tissues. t(8;14)(q24;q32) occurred at a CG dinucleotide within MYC exon 1 and at the IGHJ3 segment, and an N-like segment was inserted at the junction. The V-D-J sequence of the non-translocated IGH allele had the unmutated configuration. DNA from peripheral blood at a time of the course of MPN exhibited homozygous JAK2 ^V617F mutation, while that at BL development included both JAK2 ^V617F and wild-type DNAs. Although the association between JAK1/2 inhibitor therapy for MPN and secondary development of aggressive B-cell neoplasm remains controversial, this report suggests that, in selected patients, close monitoring of clonal B-cells in the BM is required before and during treatment with JAK1/2 inhibitors.