A case of minor BCR-ABL1 positive acute lymphoblastic leukemia following essential thrombocythemia and originating from a clone distinct from that harboring the JAK2-V617F mutation

Here we report on a case of Philadelphia chromosome positive B lymphoblastic leukemia (Ph(+)ALL), which developed following a long duration of essential thrombocythemia (ET). A mutational analysis of Janus Kinase 2 (JAK2) revealed that the V617F mutation was present in granulocytes and in hematopoietic stem and progenitor cells (HSPCs), but not in the CD34(+)CD19(+) population that mostly consists of Ph(+)ALL cells, indicating that this Ph(+)ALL clone did not originate from the ET clone carrying the JAK2-V617F mutation. The minor BCR-ABL1 fusion was detected not only in the CD34(+)CD19(+) population but also in HSPCs and granulocytes, indicating that the Philadelphia chromosome was acquired in an early hematopoietic stage at least prior to the commitment to B cell development. Upon dasatinib treatment, the minor BCR-ABL1 transcript rapidly disappeared in HSPCs but persisted in the CD34(+)CD19(+) population. A relapse of Ph(+)ALL occurred nine months later without the disappearance of the minor BCR-ABL1 transcript in the bone marrow cells during the treatment course, suggesting that a resistant Ph(+)ALL clone may have arisen or been selected in the committed B cells rather than in HSPCs. This case report may partly contribute to filling the gap between previous data acquired from mice experiments and the phenomenon in real patients.