Discovery of a novel microRNA in normal and tumor-related Human B cellsTechnology #2227
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Lead Inventors: Andrea Califano, Ph.D.; Riccardo Dalla-Favera, M.D.
MicroRNA to treat and diagnose human B cell malignancies
There is evidence that structural or functional alterations of microRNAs are associated with tumorgenesis. This technology represents a way to identify B cell malignancies and provides a method to treat a given cancer by restoring the level of microRNA expression associated with that cancer to normal. The discovery of a microRNA that is differentially expressed during normal B cell differentiation and malignant transformation has potential to transform future B cell lymphoma diagnostics and treatments.
The exact role of microRNAs in B lymphocyte development and B cell lymphomagenesis is largely unknown. These B cell subpopulations are relevant targets of disease because each can be affected by malignant transformation leading to different types of lymphomas and leukemias. A better understanding of the role of microRNAs in B cells can lead to more effective cancer treatments.
A specific and more effective method to diagnose and treat B cell derived cancers by assessing the levels of the microRNA in a given tissue and by subsequently modulating the levels of this microRNA during treatment
The microRNA discovery was made by cloning and sequencing short-RNAs (sRNAs) from three normal B cell populations (naïve B cells, germinal center (GC) B cells and memory B cells) and from a Burkitt lymphoma cell line. Bioinformatics analysis identified a novel microRNA gene present in these cell populations that was further validated by Northern blot analysis. The expression of this microRNA has a distinct pattern in normal B cells that is disrupted in the lymphoma cell line. The signature expression pattern of this microRNA can be used to identify subtypes of B cell malignancies.
– Method for down-regulating a target sequence in a cell by introducing the identified microRNA.
– Method for diagnosing whether or not a subject has or will develop a neoplasm or cancer by determining whether the expression levels of the microRNA are indicative of the presence of tumor-related human B cells.
– Method for treating human B cell lymphoma.
– MicroRNAs are known to be fundamental regulators of gene expression during development, and vital factors for maintenance of gene expression in adult tissues.
– Profiling of this microRNA may be equally or more informative in discriminating cell phenotypes than gene expression profiling.
– MicroRNAs provide novel diagnostic tools and novel treatment methods for human B cell lymphoma.
Patent information: US 2010/0197772 ~ see link below.
Licensing Status: Available for licensing and sponsored research support
K. Basso et al. Identification of the human mature B cell miRNome. Immunity, Vol. 30, Issue 5, May 2009, pp. 744-752.