A Target for the Development of Diagnostics and Therapeutics for Abnormal Hematopoiesis

The zinc finger protein ZFP36L2 has been shown by the inventors to play an essential role in hematopoiesis, a process that is dysregulated in hematological cancers, anemia, and other conditions. Thus, ZFP36L2 has promise for use in a diagnostic test to detect abnormal hematopoiesis, or as a target for the development of therapeutics to treat abnormal hematopoiesis.

Hematopoiesis is the formation of blood cellular components, through the differentiation of hematopoietic stem cells into lineages with a variety of roles, such as carrying oxygen, immune function, and blood clotting. Abnormally high hematopoiesis can be caused by hematological cancers such as leukemia or lymphoma, or by other myeloproliferative disorders. Abnormally low hematopoiesis can be caused by diseases such as anemia, thrombocytopenia, or myelodysplastic syndrome, and is often a secondary symptom of other conditions, such as cancer, infection, or dialysis.

The inventors have discovered that Zinc finger protein 36 like type-2 (ZFP36L2) plays an essential role in hematopoiesis, possibly by affecting the stability of mRNAs involved in this process. ZFP36L2 is a member of the tristetraprolin (TTP) family, which are mRNA-binding proteins involved in mRNA processing and degradation. The invention discloses methods of detecting abnormal hematopoiesis by detecting abnormal ZFP36L2 expression or a mutation in the ZFP36L2 gene, and methods of controlling abnormal hematopoiesis by modulating levels of ZFP36L2 protein.