SNPs and miRNA, Two Acronyms Used
More and More in Hematology

The Scientific Committees on Pediatric Hematology and Clinical Laboratory Hematology join together this year to provide ASH attendees a comprehensive overview on MicroRNA as a new player in hematopoiesis and cancer, and on single nucleotide polymorphisms and their clinical applications. These sessions are offered at 8:00 and 10:15 a.m., respectively, today, and again at 7:30 and 9:45 a.m. on Sunday. The MicroRNA session is chaired by Dr. Peter Newburger with Dr. Amy Pasquinelli discussing the ontogeny and phylogeny of microRNA, Dr. Chang-Zheng Chen presenting how microRNAs modulate hematopoietic lineage differentiation, and Dr. Carlo Croce summarizing the role of microRNA genes in human leukemia.

MicroRNAs (miRNAs) constitute a group of hundreds of regulatory genes encoded by the genome of multicellular organisms. In their regulatory functions, miRNAs regulate many biological processes, including hematopoiesis. Since the targets of miRNA are not well defined, neither are the mechanisms involved in miRNA-mediated gene regulation. The laboratory of Dr. Pasquinelli studies the nematode Caenorhabditis elegans in order to identify primary transcripts of specific miRNA genes to better understand how miRNAs function. In humans, miRNAs are encoded by up to 225 genes, and some are linked to human leukemias such as B cell chronic lymphocytic leukemia. The laboratory of Dr. Chen cloned about 100 miRNAs from mouse bone marrow in order to determine if any play a role in the regulation of mammalian hematopoiesis. Many miRNAs were found to be either lineage or differentiation stage specific, suggesting perhaps critical roles in hematopoiesis and differentiation. The work of Dr. Croce has focused on identifying the location of many miRNAs and has determined that, for example, miR-15a and miR-16-1 are located within a small region of loss in CLL cells suggesting an association between miRNA genes and malignancies. Other locations of different miRNAs suggest that they may play an important and unanticipated role in cancer.

The Scientific Committee on Clinical Laboratory Hematology session will discuss single nucleotide polymorphisms (SNPs) through the work of Dr. Deborah Nickerson, who will cover the background and concepts of SNPs, Dr. William Evans, who will speak about pharmacogenomics, and Dr. John Blangero, who will assess the allelic architecture of thrombosis susceptibility genes. Dr. Nickerson will provide a wide overview of SNPs and draw on available genome maps to discuss genotype-phenotype relationships. She will also discuss hotspots of recombinations and regions of natural selection in the human genome as examples of unusual patterns of variation. Dr. Evans will discuss how SNPs that have already been associated with pharmacodynamics and pharmacokinetics of many medications may play an important role in pharmacogenomics. Dr. Evans will outline his approach for utilizing pharmacogenomics for the examination of polygenic determinants of drug effects in childhood ALL, and will explain how the expression pattern of genes differentially expressed in ALL can be significantly related to treatment outcome. In his presentation, Dr. Blangero will use the example of Factor VII structural gene to describe an investigational path beginning with the localization of a human quantitative trait loci (QTL) to the complete characterization of the genetic architecture of the QTL and emphasize how this approach may lead to a comprehensive dissection of human QTLs related to disease risk. Certainly, both of these sessions will be filled with novel information and will present the audience with the latest on these two new areas of research. If SNPs and miRNAs are mysteries to you, these talks will more than get you started on these subjects; if they are familiar terms, you will have a chance to learn much more.