GFI1 as a novel prognostic and therapeutic factor for AML/MDS.

Genetic and epigenetic aberrations contribute to the initiation and progression of acute myeloid leukemia (AML). GFI1, a zinc-finger transcriptional repressor, exerts its function by recruiting histone deacetylases to target genes. We present data that low expression of GFI1 is associated with an inferior prognosis of AML patients. To elucidate the mechanism behind this, we generated a humanized mouse strain with reduced GFI1 expression (GFI1-KD). Here we show that AML development induced by onco-fusion proteins such as MLL-AF9 or NUP98-HOXD13 is accelerated in mice with low human GFI1 expression. Leukemic cells from animals that express low levels of GFI1 show increased H3K9 acetylation compared to leukemic cells from mice with normal human GFI1 expression, resulting in the upregulation of genes involved in leukemogenesis. We investigated a new epigenetic therapy approach for this subgroup of AML patients. We could show that AML blasts from GFI1-KD mice and from AML patients with low GFI1 levels were more sensitive to treatment with histone acetyltransferase inhibitors than cells with normal GFI1 expression levels. We suggest therefore that GFI1 has a dose-dependent role in AML progression and development. GFI1 levels are involved in epigenetic regulation, which could open new therapeutic approaches for AML patients.

Phosphate solubilizing microbes: sustainable approach for managing phosphorus deficiency in agricultural soils.

Phosphorus is the second important key element after nitrogen as a mineral nutrient in terms of quantitative plant requirement. Although abundant in soils, in both organic and inorganic forms, its availability is restricted as it occurs mostly in insoluble forms. The P content in average soil is about 0.05% (w/w) but only 0.1% of the total P is available to plant because of poor solubility and its fixation in soil (Illmer and Schinner, Soil Biol Biochem 27:257-263, 1995). An adequate supply of phosphorus during early phases of plant development is important for laying down the primordia of plant reproductive parts. It plays significant role in increasing root ramification and strength thereby imparting vitality and disease resistance capacity to plant. It also helps in seed formation and in early maturation of crops like cereals and legumes. Poor availability or deficiency of phosphorus (P) markedly reduces plant size and growth. Phosphorus accounts about 0.2 - 0.8% of the plant dry weight. To satisfy crop nutritional requirements, P is usually added to soil as chemical P fertilizer, however synthesis of chemical P fertilizer is highly energy intensive processes, and has long term impacts on the environment in terms of eutrophication, soil fertilility depletion, carbon footprint. Moreover, plants can use only a small amount of this P since 75-90% of added P is precipitated by metal-cation complexes, and rapidly becomes fixed in soils. Such environmental concerns have led to the search for sustainable way of P nutrition of crops. In this regards phosphate-solubilizing microorganisms (PSM) have been seen as best eco-friendly means for P nutrition of crop. Although, several bacterial (pseudomonads and bacilli) and fungal strains (Aspergilli and Penicillium) have been identified as PSM their performance under in situ conditions is not reliable and therefore needs to be improved by using either genetically modified strains or co-inoculation techniques. This review focuses on the diversity of PSM, mechanism of P solubilization, role of various phosphatases, impact of various factors on P solubilization, the present and future scenario of their use and potential for application of this knowledge in managing a sustainable environmental system.