Detection of the Acquired Tyrosine Kinase JAK2 Gene Mutation by Real Time PCR as Minimal Residual Disease Marker for Patients after Allogeneic Hematopoetic Stem Cell Transplantation.

Recently, a single point mutation (VAL617Phe) in the tyrosine kinase gene JAK2 was identified in some patients with polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis by Baxter and coworker. Here, we assessed the frequency of these acquired JAK2 gene mutations by real-time PCR in patients with myelofibrosis with myeloid metaplasia (MMM) (n=25), atypical bcr-abl negative CML (n=8), MDS (n=53), AML M6 (erythroleukaemia) (n=8) and AML megakaryocytic leukaemia) M7 (n=2) prior to a scheduled allogeneic transplant. Further, we evaluated the use of the detection of JAK2 gene mutation as a MRD marker after transplant. A JAK2 gene mutation was found in 13 of 25 patients with MMM, 1 of 8 patients with atypical CML, 2 of 2 patients with AML M7, but none in patients with MDS (n=53) or patients with AML M6 (n=8). All tested 24 healthy donors had no detectable JAK2 mutation by PCR. In 15 patients with a detectable JAK2 gene mutation prior to transplant, we evaluated the chimerism status and the detection of the JAK2 mutation by PCR simultaneously. Four of these 15 patients revealed a mixed chimerism after transplant at different time periods. In three of these four patients a JAK2 gene mutation was detectable contemporarily by PCR, whereas 11 patients with a complete chimerism detected by STR-PCR had no evidence for a JAK2 mutation at the same time point. Three patients with MMM in whom a JAK2 mutation could be detected again relapsed again of MMM. These data demonstrate that JAK2 gene mutation can be used as a MRD marker for MMM in patients who had this gene mutation prior to transplant.