Department of Medicine, Division of Hematology/Oncology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Biomark Res. 2013 Jun 6;1(1):21. doi: 10.1186/2050-7771-1-21.
BCR-ABL tyrosine kinase inhibitors (TKIs) are effective in controlling Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) are unlikely to cure the disease because TKIs are unable to eradicate leukemia stem cells (LSCs) responsible for the disease relapse even after tyrosine kinase inhibition. In addition, the TKI resistance of LSCs is not associated with the BCR-ABL kinase domain mutations. These observations indicate that TKI-insensitive LSCs and TKI-sensitive leukemic progenitor cells are biologically different, which leads us to believe that LSCs and more differentiated leukemic cells have different genetic mechanisms. Further study of LSCs to identify the novel gene signatures and mechanisms that control the function and molecular phenotype of LSCs is critical. In this mini-review, we will discuss our current understanding of the biology of LSCs and novel genes that could serve as a molecular signature of LSCs in CML. These novel genes could also serve as potential targets for eradicating LSCs in CML.
BCR-ABL 酪氨酸激酶抑制剂（TKIs）在控制费城阳性（Ph+）慢性髓性白血病（CML）方面非常有效，但不太可能治愈该疾病，因为 TKI 无法消除白血病干细胞（LSCs），而这些 LSCs 正是导致疾病复发的原因，即使在酪氨酸激酶抑制之后也是如此。此外，LSCs 的 TKI 耐药性与 BCR-ABL 激酶结构域突变无关。这些观察结果表明，TKI 不敏感的 LSCs 和 TKI 敏感的白血病祖细胞在生物学上是不同的，这使我们相信 LSCs 和更分化的白血病细胞具有不同的遗传机制。进一步研究 LSCs，以确定控制 LSCs 功能和分子表型的新基因特征和机制至关重要。在这篇迷你综述中，我们将讨论我们目前对 LSCs 生物学和可能作为 CML 中 LSCs 分子特征的新基因的理解。这些新基因也可以作为消除 CML 中 LSCs 的潜在靶点。
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