**4.2.3 NF-kB**

270 Advances in Hematopoietic Stem Cell Research

Fig. 6. LSCs main surface markers. LSCs can be defined as CD34, CD382, HLA-DR2, CD902, CD117 and CD123. The expression of CD123 seems to be leukemic-specific. Another LSC

PTEN is a phosphatase that negatively regulates signaling through the PI3K pathway, attenuating proliferation and survival signals. PTEN deficiency causes an initial expansion of normal hematopoietic stem cells due to their cycling, followed by their exhaustion. In contrast to this requirement for PTEN in the maintenance of hematopoietic stem cells, leukemic stem cells arise and expand in numbers following PTEN deletion. The observation that PTEN deletion had opposite effects on normal hematopoietic stem cells compared to leukemic stem cells raised possibility for therapeutic targeting of this pathway to eliminate only the leukemic stem cells, without affecting normal hematopoietic stem cells. Since PTEN deletion causes increased AKT and mTOR activation, it seems logical that mTOR targeting by pharmacological agents, such as rapamycin, could represent an interesting option for

specific antigen is C-type lectin-like molecule-1, CLL-1.

**4.2.2 PTEN (Akt/mTOR)** 

AML treatment (Testa, 2011).

In addition to genes involved in the control of stem cell self-renewal, leukemic stem cells are expected to express, at high levels, genes involved in anti-apoptotic mechanisms. In this context, particular attention has been focused on the study of NF-kB. NF-kB plays a critical role in inflammation, anti-apoptotic responses, and carcinogenesis. High NF-kB expression was found in primitive AML blasts. In particular, the constitutive activation of NF-kB was observed in AML cell populations enriched in leukemic stem cells, but not in normal hematopoietic stem cells. According to these observations, it seemed clear that NF-kB could be a potential therapeutic target for attempting leukemia stem cell eradication (Guzman et al., 2001).
