Introduction: What they say:
A study from the Institute of Genetics and Biophysics, CNR, Naples, Italy; and Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy shows that “miR-194-5p/BCLAF1 deregulation in AML tumorigenesis” This study was published in the 20 February 2017 issue of the journal “Leukemia” [One of the best journals in the field of “blood cancer biology” with an I.F of 12 plus] by Prof. Altuci, Dell’Aversana C, and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: ,Natural product-derived therapy for Acute Myeloid Leukemia: Myrtenal, isolated from Cardamom, decreases the expression of BCLAF1, promotes differentiation of acute myeloid leukemic cells, restores treatment responsiveness, increases therapeutic index of anticancer drugs, and promotes regression of 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 is one of the most predominant leukemias among all adult leukemias; (v) each year about 10, 500 and 2900 new cases of AML are reported in the US and the UK, respectively; (vi) cure rates of AML ranges from 20-45% only, 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. Altucci’s research team has recently shown that MiRNA miR-194-5p: (1) inhibits BCL2-associated transcription factor 1 (BCLAF1) expression; (2) aids BCLAF1 in shuttling between nucleus and cytosol; (3) and its target gene BCLAF1 are commonly dysregulated in primary AMLs; (4) is induced in response to the HDAC inhibitor SAHA treatment, promotes differentiation, induces apoptosis and restores treatment responsiveness, suggesting that induction of miR-194-5p; and downregulation of its down-stream target gene BCLAF1 in AML cells may prevent AML progression.
From research findings to therapeutic opportunity :
This study suggests a natural product-derived anticancer therapy. Myrtenal, one of the main components of Cardamom, is known to function as an anticancer agent (fig. 1). However, the detailed mechanistic insights is yet to emerge.
Myrtenal, by increasing the expression of its target genes, it may increase the expression of miR-194-5p (fig. 1). Thereby, it may: (i) decrease the expression of BCLAF1; (ii) aid BCLAF1 in shuttling between nucleus and Cytosol; (iii) promote differentiation of acute myeloid cells; (iv) restore treatment responsiveness; (v) increase therapeutic index of anticancer drugs; (vi) inhibit AML growth; and (vii) promote AML regression (fig.1).
Thus, pharmacological formulations encompassing “Myrtenal or its analogues, either alone or in combination with other known anticancer drugs” (fig. 2), may be used to inhibit AML growth.
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Undisclosed mechanistic information: How does Myrtenal decrease the expression of BCLAF1 to inhibit AML growth?
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Citation: Boominathan, L., Natural product-derived therapy for Acute Myeloid Leukemia: Myrtenal, isolated from Cardamom, decreases the expression of BCLAF1, promotes differentiation of acute myeloid leukemic cells, restores treatment responsiveness, increases therapeutic index of anticancer drugs, and promotes regression of AML via up-regulation of its target gene, 19/May/2017, 12.06 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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