Zeev Estrov, M.D. University of Texas MD Anderson Cancer Center

CLL-STROMA INTERACTION

Role of STAT3 in CLL

Grant Awarded in 2008

Abstract:

CLL growth and survival is impacted by signals within the CLL cell. In the bone marrow, certain signals cause the CLL cells to undergo "spontaneous" death. Recently, we identified an intracellular signaling protein, STAT-3, that stimulates CLL cell growth and survival. (STAT-3 has a similar activation effect in other leukemias).

Specific inhibitors of STAT-3 suppress CLL cell proliferation and kill CLL cells. Interleukin-6, a cytokine or regulatory protein derived from bone marrow cells, appears to counteract the inhibitor effect thereby keeping the CLL cells alive. Therefore, we asked whether external signals such as cytokines would hamper the effects of STAT-3 inhibitors.

To answer this question, we will conduct experiments with CLL bone marrow cells, normal cells and outside growth factors. We will explore how bone marrow-supportive cells "fight" CLL cells. Our hypothesis is that bone marrow supportive cells recognize an expanding population of CLL cells and generate factors to stop cell growth. While cytokines may be capable of killing CLL cells, they might also suppress normal cells thereby inducing low blood count in patients with CLL.

We will investigate how the bone marrow responds to a growing clone of CLL cells, and whether CLL marrow supports and stimulates the development of precursor cells. Understanding the roles of these factors in maintaining CLL cells will allow us to development future CLL treatments.