Germline mutations in the MEN1 gene encoding menin protein cause multiple endocrine neoplasia type 1 (MEN1) syndrome. Recent evidence suggests that inhibiting the interaction of menin with its crucial oncogenic protein partners represents a promising therapeutic strategy to AML. Menin plays a critical role in lysine methyltransferase 2A (KMT2A)-gene-rearranged and NPM1-m acute leukemias, both associated with adverse outcomes with current standard therapies, especially in the relapsed/refractory setting. Disrupting the menin–KMT2A interaction affects the proleukemogenic HOX/MEIS transcription program. This disruption leads to the differentiation of KMT2Ar and NPM1-m AML cells. Small molecular inhibitors of the menin–KMT2A interaction target the central cavity of MEN1 to inhibit the MEN1-KMT2A interaction and could target a similar transcriptional dependency in other leukemia subsets, broadening their therapeutic potential. These agents, both as monotherapies and in combination with synergistic drugs, are undergoing preclinical and clinical evaluation with promising early results. With the growing literature around menin inhibitors in AML, we discussed the biology of menin, its mechanism of action, its interacting partners in leukemia, possible inhibitors, their implications, synergistic drugs, and future therapeutic strategies in this review.
Here we examine the effects of different carrier based bioinoculants on the growth, yield and nutritional value of chickpea and on associated soil nutrients. A consortium of two taxonomically distinct endophytic bacteria—Ensifer adhaerens MSN12 and Bacillus cereus MEN8—have promising plant growth promoting (PGP) attributes. We demonstrate their delivery from the laboratory to the field via the formulation of an effective bioinoculant with economic and accessible carriers. Sugarcane straw ash (SCSA) was found to be an efficient carrier and bioformulation for enhancing viability and shelf-life of strains up to 12 months. A bioformulation containing an SCSA-based consortium (MSN12 + MEN8) increased seed germination by 7%, plant weight by 29%, length by 17%, seed-yield by 12%, harvesting index by 14% and proximate nutritional constituents by 20% over consortium treatment without SCSA. In addition, the bioformulation of post-harvest treated soil improved the physico-chemical properties of the soil in comparison to a pre-sowing SCSA-based bioformulation treated crop, being fortified in different proximate nutritional constituents including dry matter (30%), crude protein (45%), crude fiber (35%), and ether extract (40%) in comparison to the control. Principal component analysis and scattered matrix plots showed a positive correlation among the treatments, which also validates improvement in the soil nutrient components and proximate constituents by T6 treatment (MSN12 + MEN8 + SCSA). The above results suggest efficiency of SCSA not only as a carrier material but also to support microbial growth for adequate delivery of lab strains as a substitute for chemi-fertilizers.