Loss of STAT3 in NK cells promotes the death of tumor cells

Health, the biggest fortune of human being, is so valuable through one's entire life from birth to death. But judgement of health is not so fair for the ones with genetic deficiency who are sentenced to suffer from high possibilities of genetic diseases. With the leading technology of MALBAC, Chinese scientists give a couple the right to make sure that their baby is born without the unfair judgement. Human being paces in a new era of reproductive health, and much more important is that a family could avoid a possible tragedy.

Early in the end of 2012, Sunney Xie Team from Harvard university reported the MALBAC technology. It is abbreviation for "Multiple Annealing and Looping-Based Amplification Cycles". MALBAC utilizes ingenious primer design to make amplicons bearing complementary ends and looping, preventing DNA from exponentially amplification. So, in the soul of technology, MALBAC is much fair and present the whole genome in reduced amplication bias.

Thanks to the Malbac, the genome coverage of single human cell sequencing achieved 93%, and very little template DNA is required. That means more efficient single cell sequencing. Scientists from Dr. Jie Qiao's group, Sunney Xie's group and Fuchou Tang's group used MALBAC to screen healthy embryos to protect off springs from their parents' hereditary disorder. In this case, the husband suffers from Hereditary Multiple Exostoses, an autosomal dominant hereditary disorder which has a 50% chance of transmitting this disorder to his children. To avoid this risk, total 18 embryos at blastcyst stage were obtained during IVF cycle. A few cells were biopsied from each embryo for amplification using MALBAC method. Combined with the targeted PCR and next generation sequencing techniques, all the numerical and structural chromosome abnormalities and the mutated allele of the genetic disease were accurately detected with low depth sequencing data(0.1x). Three embyos were identified to be free of inherited mutated allele and chromosome copy number abnormalities, and one healthy embryo of the three was transfered back to the wife. Several days ago, the baby was born successfully, with 4.03 kg of weight and 53 cm of length. Umbilical cord blood genome detection confirmed the baby is free of the mutated allele, and free from unfair judgement.

Dagmar Gotthardt1 and Eva M. Putz1 findings imply that STAT3 inhibitors will stimulate the cytolytic activity of NK cells against leukemia, thereby providing an additional therapeutic benefit, and this data was published on the journal of blood in 2014.

The members of the signal transducer and activator of transcription (Stat) family of transcription factors modulate the development and function of natural killer (NK) cells. NK cell–mediated tumor surveillance is particularly important in the body’s defense against hematological malignancies such as leukemia. STAT3 inhibitors are currently being developed, although their potential effects on NK cells are not clear. In the absence of STAT3, NK cells develop normally and in normal numbers, but display alterations in the kinetics of interferon-? (IFN-?) production. In various in vivo models of hematological diseases, loss of STAT3 in NK cells enhances tumor surveillance. The reduced tumor burden is paralleled by increased expression of the activating receptor DNAM-1 and the lytic enzymes perforin and granzyme B.