MUTANT JAK3 KINASE IN HUMAN LEUKEMIA

摘要

In accordance with the invention, a novel activating mutation (alanine 57 2 to valine) in JAK3 kinase has been discovered in human acute myelogenous l eukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferati on and survival of acute megakaryoblastic leukemia (AML-M7). The invention t herefore provides, in part, isolated polynucleotides and vectors encoding th e disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolat ed mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant pr otein and enables new methods for determining the presence of mutant JAK3 ki nase polypeptides in a biological sample, methods for screening for compound s that inhibit the mutant proteins, and methods for inhibiting the progressi on of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.