Research ArticleAcute Myeloid Leukemia

A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivo

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Science Translational Medicine  17 Apr 2013:
Vol. 5, Issue 181, pp. 181ra52
DOI: 10.1126/scitranslmed.3004387

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Taking AML Head-On

Like the mythic Lernaean Hydra, acute myeloid leukemia (AML) is hard to kill. It seems like every time one head is cut off, another two—meaner—grow back in its place. Leukemia stem cells (LSCs) are thought to contribute to this resilience; they may survive conventional chemotherapy and increase the risk of relapse. However, it has been difficult to specifically target these cells without also hitting the normal hematopoietic stem cells (HSCs) required for maintaining healthy blood cells. Now, Saito et al. find a new candidate drug that can specifically target LSCs.

The authors performed a chemical library screen to target hematopoietic cell kinase (HCK), which they had previously found to be differentially expressed in human LSCs compared with HSCs. They found a candidate HCK inhibitor, RK-20449, which is a pyrrolo-pyrimidine derivative that could bind the active pocket of HCK. In a mouse xenograft of aggressive human AML, RK-20449 greatly reduced LSC burden. If these studies hold true in patients, RK-20449 could accomplish the Herculean task of decreasing the risk of relapse in AML.

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