In someone with an asymptomatic JAK2 V617 mutated and BCR/ABL negative MPN with a steadily rising WBC, when do you decide to start cytoreductive therapy and which agent(s) do you recommend?

First, let's abandon the phase "BCR/ABL-negative MPN". This is an oxymoron because BCR/ABL can be expressed in a JAK2 driver mutation-positive MPN. In fact, both BCR/ABL and JAK2 mutations can be expressed in normal individuals at very low levels without causing disease. Both mutations can also be present in MPN patients but the BCR/ABL mutation expression is much lower than JAK2 V617F expression. This is why qualitative PCR assays for MPN driver mutations are misleading. A quantitative assay for the MPN driver mutation allele burden is mandatory diagnostically, prognostically, and therapeutically. This is a blood sample assay and usually part of an NGS or leukemia panel screen. Using a quantitative allele burden assay is not necessary for ...