**6.4 Immunophenotype of LSCs**

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

**21**

*Advances in Acute Myeloid Leukemia Stem Cells DOI: http://dx.doi.org/10.5772/intechopen.84263*

effect in the AML mouse model [22].

immunophenotype of LSCs.

**7. Summary**

in future.

**Acknowledgements**

QNRC2016833).

against CD33<sup>+</sup>

a good candidate for selective killing of CD33<sup>+</sup>

years, tumor-specific chimeric antigen receptor T-cell immunotherapy (CART)

that the anti-CD123 monoclonal antibody CSL362 has a good tumor cell killing

achieved initial clinical success, it is undeniable that LSCs are diverse among different patients, and even in the same individual, the phenotypic differences are quite different. This brings new challenges to clinical treatment. Moreover, studies have shown that in patients with newly diagnosed AML, the distribution of LSCs is uniform and the number is small, but once the patient relapses after chemotherapy, the number of LSCs can be significantly increased, and some new phenotypes appear [97]. The phenotypic changes in LSCs at different stages of the same patient's disease also lead to difficulties in clinical application of this targeted LSC immunophenotypic treatment strategy. Therefore, the current targeted therapy based on this strategy is still in the exploration stage, and the development of related drugs is significantly limited due to the plasticity of the

Although the current monoclonal antibodies against the LSCs phenotype have

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

The authors acknowledge financial support from the National Natural Science Foundation of China (Grant no. 81502663), Social Development Foundation of Zhenjiang City (Grant no. SH2018063), Six talent peals project of Jiangsu Province (Grant no.WSW-039), Six for one project of Jiangsu Province (Grant no. LGY2018093), Young medical talents of Jiangsu (Grant no.

cells has become increasingly popular [96]. Busfield et al. detected

LSCs [95]. In addition, in recent

*Advances in Acute Myeloid Leukemia Stem Cells DOI: http://dx.doi.org/10.5772/intechopen.84263*

a good candidate for selective killing of CD33<sup>+</sup> LSCs [95]. In addition, in recent years, tumor-specific chimeric antigen receptor T-cell immunotherapy (CART) against CD33<sup>+</sup> cells has become increasingly popular [96]. Busfield et al. detected that the anti-CD123 monoclonal antibody CSL362 has a good tumor cell killing effect in the AML mouse model [22].

Although the current monoclonal antibodies against the LSCs phenotype have achieved initial clinical success, it is undeniable that LSCs are diverse among different patients, and even in the same individual, the phenotypic differences are quite different. This brings new challenges to clinical treatment. Moreover, studies have shown that in patients with newly diagnosed AML, the distribution of LSCs is uniform and the number is small, but once the patient relapses after chemotherapy, the number of LSCs can be significantly increased, and some new phenotypes appear [97]. The phenotypic changes in LSCs at different stages of the same patient's disease also lead to difficulties in clinical application of this targeted LSC immunophenotypic treatment strategy. Therefore, the current targeted therapy based on this strategy is still in the exploration stage, and the development of related drugs is significantly limited due to the plasticity of the immunophenotype of LSCs.
