Cancer specialists at City of Hope have developed a new test that can detect a genetic mutation found in most patients with certain myeloproliferative disorders, providing a more advanced, specific way to diagnose those conditions.
The Division of Pathology’s molecular diagnostic laboratory came up with an assay that can detect whether genetic matter from blood or bone marrow samples contains a specific mutation in the Janus kinase 2 gene, or JAK2. They developed an allele-specific polymerase chain reaction followed by separation and detection with capillary electrophoresis, and used blood and bone marrow specimens provided by City of Hope hematologic oncologist David Snyder, M.D., as well as some from Stanford University researchers, to validate the test.
Myeloproliferative disorders include Philadelphia chromosome-positive chronic myelogenous leukemia as well as polycythemia vera, a stem-cell disorder that results in too many red blood cells, essential thrombocythemia, a disorder in which the body makes too many platelets, and myelofibrosis, a bone-marrow disease resulting in marked marrow fibrosis, enlargement of the spleen and marrow failure. Unfortunately, such diseases are often initially confused with other non-neoplastic blood disorders such as reactive leukocytosis and thrombocytosis.
"With exception of chronic myelogenous leukemia, in most myeloproliferative disorders, we have no specific genetic or cytogenetic abnormality we can test for, and a diagnosis must be made on the basis of clinicopathologic correlation," said Qin Huang M.D., Ph.D, a hematopathologist and director of the hematopathology laboratory. "Having a genetic test should greatly improve our diagnosis and patient care."
Nearly a year ago, separate research teams at Cambridge Institute for Medical Research in England and Brigham and Women’s Hospital in Boston each reported that many patients with myeloproliferative disorders carried a single, important mutation in JAK2. The Cambridge team reported finding the mutation in 97 percent of polycythemia vera patients, 57 percent of essential thrombocythemia patients and 50 percent of myelofibrosis patients they tested; the Brigham and Women’s team published similar results.
As a tyrosine kinase, the JAK2 gene product plays a key role in the signaling pathway that controls the production and regulation of hematopoietic (blood) cells. Ultimately, researchers hope that agents will be developed to inhibit JAK2 much in the same way Gleevec inhibits the tyrosine kinase behind chronic myelogenous leukemia.
Huang noted that several labs have performed their own tests for JAK2 mutations, but they are spread throughout the country. The City of Hope laboratory provides a local option for Los Angeles-area physicians who seek additional testing for their patients with myeloproliferative disorders.
"Outside institutions can send us samples for analysis," said Huang. The laboratory is located in the Northwest Building. Anyone interested in the test may call Huang's lab at ext. 63564 (or 626-256-HOPE, ext. 63564, from outside City of Hope).