Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph+ B cells but not bone marrow stem/progenitors
Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph+ B cells but not bone marrow stem/progenitors
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利用基因组下一代测序技术检测慢性粒细胞白血病的残留疾病揭示了分化的Ph+ B细胞而不是骨髓干/祖细胞的持久性
DOI：
10.1080/10428194.2020.1837366
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发表时间：
2020-10
影响因子：
2.6
通讯作者：
Daiki Karigane;H. Kasahara;Kouhei Shiroshita;S. Fujita;Hiroshi Kobayashi;Shinpei Tamaki;R. Yamazaki-
中科院分区：
文献类型：
--
作者：
Daiki Karigane;H. Kasahara;Kouhei Shiroshita;S. Fujita;Hiroshi Kobayashi;Shinpei Tamaki;R. Yamazaki-
摘要白血病干细胞（LSC）的持续存在导致慢性粒细胞白血病（CML）在给予酪氨酸激酶抑制剂（TKI）后复发。因此，检测具有LSC潜力的微小残留病（MRD）可以改善预后。在这里，我们分析了115例CML患者，发现CD 25优先在表型干细胞和祖细胞（SPC）上表达，TKI治疗减少了SPC部分中CD 25阳性细胞的数量。为了检测携带BCR-ABL 1融合DNA的MRD，我们开发了一种使用患者特异性引物和下一代测序的高灵敏度方法。通过使用这种方法，我们发现在达到分子缓解的患者中，几乎所有残留的CD 25阳性SPC都是BCR-ABL 1阴性的。此外，在一些患者中，BCR-ABL 1在外周B细胞中可检测到，但在SPC中不可检测到。我们得出的结论是，CD 25在诊断时标记LSC，但在TKI治疗后不标记MRD，并且外周B细胞分析可以灵敏地检测MRD。
Abstract Persistence of leukemic stem cells (LSCs) results in the recurrence of chronic myeloid leukemia (CML) after the administration of tyrosine kinase inhibitors (TKIs). Thus, the detection of minimal residual disease (MRD) with LSC potential can improve prognosis. Here, we analyzed 115 CML patients and found that CD25 was preferentially expressed on the phenotypic stem and progenitor cells (SPCs), and TKI therapy decreased the number of CD25-positive cells in the SPC fraction. To detect MRD harboring BCR-ABL1 fusion DNA, we developed a highly-sensitive method using patient-specific primers and next-generation sequencing. By using this method, we identified that in patients who achieved molecular remission, almost all residual CD25-positive SPCs were BCR-ABL1-negative. Moreover, in some patients BCR-ABL1 was detectable in peripheral B cells but not in SPCs. We conclude that CD25 marks LSCs at diagnosis but does not mark MRD following TKI treatment and that analysis of peripheral B cells can allow sensitive detection of MRD.