An acquired somatic mutation in the JAK2 gene (JAK2-V617F) is frequently found in patients with myeloproliferative disorders (MPD). In most studies the JAK2-V617F mutation has been analyzed at single time point. Here we performed a retrospective single center study on 73 MPD patients (36 polycythemia vera (PV), 29 essential thrombocythemia (ET), and 8 primary myelofibrosis (PMF)) from whom at least two blood samples (mean=5, range 2–17) were available with an interval of at least 8 months. The mean follow-up period was 35±17 months (range 8–78 months). The allelic ratio of JAK2-V617F (%T) was determined in DNA from purified peripheral blood granulocytes by allele-specific PCR. In 73 MPD patients studied, 53 (73%) carried the JAK2-V617F mutation (32 PV, 18 ET, 3 PMF). None of the 20 patients negative for JAK2-V617F acquired the JAK2-V617F mutation during the observation period (n=20, mean number of samples=4). In the majority of the JAK2-V617F positive patients (35/53; 66%) the JAK2-V617F allelic ratios remained remarkably stable during the follow-up period (variation ±5%T) (Figure 1 A and B). In 10/53 patients (19%) we observed an increase and in 8/53 (15%) a decrease in JAK2-V617F allelic ratio greater than 5%T. Interestingly, 3/10 patients (1 ET and 2 PV) who showed increase of JAK2-V617F developed secondary myelofibrosis. Twenty six patients (49%) received cytoreductive treatment (hydroxyurea: 24, interferon alpha: 1, anagrelide: 1). Cytoreduction with hydroxyurea did not significantly reduce the JAK2-V617F allelic ratios (Figure 1A) compared to untreated patients (Figure 1B). The only molecular remission was seen in one patient treated with interferon alpha (Figure 1 A). In one patient without cytoreduction JAK2-V617F became undetectable because of transformation to acute myeloid leukemia with blast cells negative for JAK2-V617F. A second patient treated with hydroxyurea showed a pronounced decrease of JAK2-V617F (–47%T in 6 months), but no clinical or laboratory signs of leukemic transformation were present. We conclude that the amount of JAK2-V617F remains very stable in a majority of JAK2-V617F positive patients. Prospective studies will help to elucidate whether increasing JAK2-V617F allelic ratios can predict secondary myelofibrosis or decreasing allelic ratios in absence of cytoreductive therapy (e.g. interferon alpha) are early signs of leukemic transformation.

Figure 1A.
Figure 1A.
View largeDownload slide
Figure 1B.
Figure 1B.
View largeDownload slide
Topics:
jak2 gene v617f, mutation, myeloproliferative disease, hydroxyurea, interferon-alpha, debulking, follow-up, secondary myelofibrosis, anagrelide, cytoreductive therapy

Author notes

Disclosure: No relevant conflicts of interest to declare.

2007, The American Society of Hematology
2007
Sign in via your Institution