Burkitt leukemia with precursor B-cell features that developed after ruxolitinib treatment in a patient with hydroxyurea-refractory JAK2V617F-myeloproliferative neoplasm

摘要

A 62-year-old woman, who had a 16-year history of JAK2 supV617F/sup-mutated myeloproliferative neoplasm (MPN), developed Burkitt leukemia (BL) 16 months after treatment with ruxolitinib to control hydroxyurea-refractory conditions. BL cells were CD10sup+/sup, CD19sup+/sup, CD20sup?/sup, CD34sup?/sup, cytoplasmic CD79asup+/sup, and TdTsup+/sup, and lacked surface immunoglobulins but expressed the cytoplasmic μ heavy chain. In the bone marrow, nuclear MYCsup+/sup 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 supV617F/sup mutation, while that at BL development included both JAK2 supV617F/sup 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.