title: 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.
abstract: 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.
authors: Yuya
authors: Y
authors: Nagai
authors: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. machakm6@kuhp.kyoto-u.ac.jp.
authors: Masahiro
authors: M
authors: Kawahara
authors: Noriko
authors: N
authors: Sugino
authors: Yayoi
authors: Y
authors: Shimazu
authors: Masakatsu
authors: M
authors: Hishizawa
authors: Kouhei
authors: K
authors: Yamashita
authors: Norimitsu
authors: N
authors: Kadowaki
authors: Akifumi
authors: A
authors: Takaori-Kondo