Introduction: What they say:
A study from the Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; and Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA shows that “The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia.” This study was published, in the 13 February 2017 issue of the journal “Nature Medicine” [the number 1 journal in General Medicine with an I.F of 30.357], by Prof. Stegmaier Kimberly, Fenouille N, and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Combinatorial therapy for EVI-1-Overexpressing Acute Myeloid Leukemia: a therapeutic mix encompassing Simvastatin and Navitoclax/ABT-263 (SAN) decreases the expression of MECOM/EVI-1 and its down target genes, including CKMT-1, alters Arginine-creatine metabolism, inhibits mitochondrial respiration, depletes ATP levels, and promotes regression of EVI-1-overexpressing AML via up regulation of its target gene
From Significance of the study to Public health relevance:
Given that: (i) each year nearly 14 million people are diagnosed with cancer globally, and little more than half of them will die; (ii) cancer deaths globally are expected to be doubled by 2030; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide; (iv) Acute myeloid leukemia (AML) is one of the most predominant leukemias among all the adult leukemias; (v) each year about 10, 500 and 2900 new cases of AML are reported in the US and the UK, respectively; (vi) complete cure from AML is possible only in 20-45% cases, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and prevent metastatic progression and relapse of cancers.
What we infer from what they say:
Prof. Stegmaier Kimberly’s research team has recently shown that: (1) oncoprotein MECOM (MDS1 And EVI1 Complex Locus, also known as EVI1) suppresses the expression of myeloid differentiation regulator Runx1 [(Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1)]; (2) increases the expression of the ATP-buffering, mitochondrial creatine kinase CKMT1; (3) inhibition of CKMT1 promotes cell cycle arrest, induces apoptosis of human EVI1-expressing AMLs; and promotes survival in mouse models of primary AMLs. Further, they shown that inhibition of CKMT1 results in (1) altered mitochondrial respiration; and (2) reduction in ATP levels, suggesting that suppressing CKMT in EVI1-driven AML may stall its progression. Together, these findings suggest that inhibition of EVI-1 and its downstream target gene CKMT1 expression in AML cells may prevent AML growth.
From research findings to therapeutic opportunity :
This study suggests a combinatorial therapy for cancer. This study suggests, for the first time, that Simvastatin and Navitoclax/ABT-263 (SAN), by decreasing the expression of its target genes, it may inhibit the expression of MECOM/EVI-1 and its downstream target gene CKMT1 (fig. 1).
Thus, pharmacological formulations encompassing “Simvastatin and Navitoclax/ABT-263 (SAN) or their analogues, either alone or in combination with other known anticancer drugs,” may be used to inhibit AML progression.
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Undisclosed mechanistic information: How does Simvastatin and Navitoclax/ABT-263 (SAN) decrease the expression of EVI-1 and its downstream target gene CKMT1 ?
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Citation: Boominathan, L., Combinatorial therapy for EVI-1-Overexpressing Acute Myeloid Leukemia: a therapeutic mix encompassing Simvastatin and Navitoclax/ABT-263 (SAN) decreases the expression of MECOM/EVI-1 and its down target genes, including CKMT-1, alters Arginine-creatine metabolism, inhibits mitochondrial respiration, depletes ATP levels, and promotes regression of EVI-1-overexpressing AML via up regulation of its target gene, 3/March/2017, 11.23 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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