In a courtroom drama, sometimes the facts are so cut and dried that the defendant’s fate is all but sealed. New research from Marina Bousquet, a Lodish lab member at the Whitehead Institute, makes a strong case that miR-125b is essentially a smoking gun that causes leukemia.
miR-125b is overexpressed in several different types of leukemias including acute lymphoblastic leukemia (ALL) and it’s been reported to give progenitor hematopoietic cells a competitive advantage, perhaps by targeting apoptosis gene transcripts. It’s also known to target the p53 pathway, and probably others as well. So, is miR-125b’s upregulation a cause or effect?
Bousquet tackled that question by transplanting irradiated mice with fetal liver cells overexpressing miR-125b. All the mice showed increased white blood cell counts, and half of them ended up with either B-cell ALL, T-cell ALL or a myeloproliferative disorder neoplasm.
Then she reconstituted another set of mice with bone marrow expressing the BCR-ABL fusion gene (a model for leukemia), some co-expressing miR-125b. The mice with miR-125b developed leukemia much faster than those with just the BCR-ABL, pointing the finger at miR-125b as a key instigator of leukemias that acts either alone or with other factors like BCR-ABL.
It sure looks like miRNA-125b got caught red-handed; find out if it can beat the rap in PNAS Online, November 2010.