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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.
Authors: Nagai, Yuya
Kawahara, Masahiro
Sugino, Noriko
Shimazu, Yayoi
Hishizawa, Masakatsu
Yamashita, Kouhei
Kadowaki, Norimitsu
Takaori-Kondo, Akifumi
Author's alias: 河原, 真大
Keywords: JAK2-V617F
Myeloproliferative neoplasms
BCR-ABL1
Lymphoblastic leukemia
Tyrosine kinase inhibitor
Resistant clone
Issue Date: 17-Feb-2014
Publisher: BioMed Central Ltd.
Journal title: Experimental hematology & oncology
Volume: 3
Issue: 1
Thesis number: 6
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.
Rights: © 2014 Nagai et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
URI: http://hdl.handle.net/2433/185221
DOI(Published Version): 10.1186/2162-3619-3-6
PubMed ID: 24528501
Appears in Collections:Journal Articles

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