FOXP3遺伝子TSDR領域の低メチル化は、成人T細胞白血病における制御性T細胞サブタイプの特徴である。

京都大学0048新制・課程博士博士(医学)甲第19626号医博第4133号新制||医||1016(附属図書館)32662京都大学大学院医学研究科医学専攻(主査)教授 生田 宏一, 教授 清水 章, 教授 河本 宏学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

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