Scientists from the Univ. of Cincinnati College of Medicine showed in their research paper published in the June 10th issue of Cancer Cell that CD34+ expressing the MLL-AF9 gene could be induced into forming acute myeloid, lymphoid, and mixed-lineage leukemia in immunodeficient mice. The study results revealed the presence of multipotent leukemia stem cells (LSC) of which the type of leukemia was dependent upon the cues within the microenvironment. The study results revealed that growth factors which induced differentiation of hematopoietic progenitor cells had an important role for determining whether the MLL-AF9 cells progressed to either an acute lympoid leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML). Additionally, in vivo experiments further demonstrated that the cues from the microenvironment determined the phenotype of the leukemia. In NS-SGM3 mice receiving the MLL-AF9 cells, the animals developed AML 5-7 weeks after transplantation. In NS strain of mice, ALL and AML developed after transplantation of MLL-AF9 cells. The investigators also found that by targeting the Rac signaling pathway, they were able to induce apoptosis in the cells expressing the MLL-AF9 protein. The authors concluded that drugs which targeted inhibition of Rac signaling may be used in the future to treat patients with these forms of leukemias.

Scientists from Harvard Medical School, K. Ito et al., reported in the May 11th online edition of Nature the results of their study on identifying a promyelocytic leukemia protein that maintains the quiescent state leukemia-initiating cells (cancer stem cells) and the potential to target the protein in order to eradicate this subpopulation of cells (possibly through activation and differentiation of the quiescent cells). The investigators noted that their study is based on the premise that the existent of a quiescent population of self-renewing cancer-initiating cells may correlate with drug resistance to chemotherapy as well as targeted therapies. The investigators hypothesized that this quiescent state allows the cells to escape current therapeutic regimens which may explain the observation of the high incidence of relapses in leukemias such as chronic myeloid leukemia (AML). It was further noted that inability to eradicate these leukemia-initiating cells by current therapies leads to disease relapses when there is a discontinuation of a drug. The investigators presented data that the PML-associated protein maintains the pool of these quiescent leukemia-initiating cells. By targeting the PML protein, the authors concluded from their experimental data that such an approach may eventually evolve into novel pharmacological therapies that not only eradicate the quiescent leukemia-initiating cells, but they may actually cure the disease.