**7. Summary**

*Advances in Hematologic Malignancies*

**6.3 Cell cycle of LSCs**

**Figure 2.**

proliferation [94].

**6.4 Immunophenotype of LSCs**

In patients with drug resistance, most of their LSCs are in the quiescent phase

*The niche of leukemic stem cell. The niche provides support for self-renewal, quiescence, homing, engraftment, and proliferative potential for HSCs. LSCs may impair the function of the normal HSC niche. In addition,* 

(G0 phase) and therefore cannot be effectively eliminated by chemotherapy. Hence, some people consider that LSCs in stationary phase can be eliminated by two-step method: (1) Stimulate LSCs from the G0 phase into the cell cycle proliferation and then use specific tumor-targeted therapeutic drugs to eliminate LSCs and (2) Let LSCs stay in the G0 phase. It is worth noting that although the cells in the G0 phase are dormant, they have the ability to proliferate; thus, this can only delay survival and avoid recurrence. Experiments in vitro have shown that cyclin-dependent kinase (CDK6) can be involved in the regulation of cell cycle, and inhibition of CDK6 may cause leukemia stem cells to dormant and inhibit cell

*LSCs can infiltrate these niches and may hijack these normal homeostatic processes.*

Several immunophenotypes of LSCs have been identified, such as CD34, CD38, CD123, CD117, CD71, CD44, HLA-DR, TIM3, CLL-1, CD96, CD47, CD32 and CD25. Although these surface molecules are not expressed in all LSCs, their high expression may lead to a significant deterioration of the disease prognosis. It is also because of the difference in markers and functions between LSCs and HSCs that targeted therapy for leukemia stem cells is possible. CD33 is the first AML targeted therapeutic antigen approved by the US FDA, which is highly expressed in AML but not in normal HSCs. The monoclonal anti-tumor drug Gemtuzumab ozogamicin, consisting of the CD33 antibody, hP67.6, and the cytotoxic drug, is

**20**

LSCs play an important role in the origin, recurrence, and drug resistance of leukemia. Although the current research on LSCs has made some progress, the biological characteristics of LSCs and its mechanism in the pathogenesis of leukemia remain unclear, and the treatment strategy for targeted clearance of LSCs is still in its infancy. Therefore, clarifying its biological characteristics and developing drugs for targeted therapy of LSCs is an important direction for leukemia research in future.
