Implications of Molecular Estimation of Allelic Burden of JAK2 V617F Mutant Allele in Essential Thrombocythemia and Polycythemia Vera Diseases

Aims: Development of a JAK2 Allelic burden estimation kit using Taqman probes and determine trend in shifting of JAK2 V617F allelic burden in and its use in analysis of patients with essential thrombocythemia (ET) and polycythemia vera (PV) to predict thrombotic complications.

Methodology: Through a retrospect study, a total of 412 ET and PV patient, divided into 3 groups (0-2, 2-5 and 5-10 years) based on time of detection of the disease, were tested in retrospect for presence of the JAK2 V617F mutant allele burden using an in-house developed Taqman probe-based kit, trend in shifting of the mutant allele burden was studied and segregated into ET (n=167) and PV (n=126) group based on their disease profile. It was then categorized into 3 time periods (0-2, 2-5 and 5-10 years) based on time of detection of the disease.

Results: Around 293 (71%) were positive for JAK2 V617F while 59 (14.2%) and 8 (1.9%) positive for CALR exon 9 frame shift & MPL mutations (W515L/W515K) respectively. The 1-25% allelic burden group size gradually fell in ET population over time and this trend continued in the PV population also. In the former the fall was 7% & 11% for 2-5 & 5-10 years category while in the later, it was 1% and 15% respectively for the same time period-category.

Conclusions: There is a distinct molecular continuum in the JAK2 V617F allelic burden in the ET & PV patients which followed a predictable trend and was associated with increasingly complicated vascular events.