Correlation of JAK2 V617F Mutation Burden with Clinical and Hematologic Characteristics of Myeloproliferative Neoplasms
Alan F Brown, Yao Wang, Misty M Abu-Ghusson, Princess A George, Kumari Vadlamudi, Weislaw B Furmaga, Hongxin Fan. University of Texas Health and Science Center, San Antonio, TX
Background: Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (MF) exhibit a high proportion of acquired JAK2 V617F mutation. Mutation burden (MB) may be closely related to the type, stage, and prognosis of the MPN. We studied the correlation of JAK2 V617F MB tested by real-time quantitative allele-specific (RT-QAS) PCR with clinical and hematologic characteristics of PV, ET, and MF patients.
Design: Of 356 blood and bone marrow (BM) samples screened for JAK2 mutation due to abnormal hematologic findings, 36 cases were with elevated JAK2 V617F MB. JAK2 V617F MB were detected by RT-QAS PCR assay utilizing a single set of primers combined with two TaqMan MGB probes that target either wild-type or mutant JAK2 alleles, respectively. Assay was performed on ABI 7900HT instrument (Applied Biosystems). Retrospective clinical and laboratory information including clinical presentation, type of MPN, hemoglobin level, white blood cell and platelet counts, spleen size, and vascular complications were evaluated on all 36 JAK2 mutation positive cases. Additionally, 10 cases with repeated JAK2 testing performed in different time points were evaluated for disease progression and change in MB.
Results: Clinical, laboratory and JAK2 MB is compiled in Table 1. By correlation study, MB was positive correlated to leukocyte count (R2=0.544; p<0.05) in all patients; to BM cellularity (R2=0.379; p<0.05) in ET patients (n=17); and to platelet counts (R2=0.335; p<0.05) in PV patients (n=11). No correlations were identified between MB and other parameters (BM fibrosis, splenomegaly, vascular event, or age). Ten patients underwent interval repeat JAK2 quantification that displayed a mean increase of 3.81% (range -2 to 20.07%) in MB over a mean interval of 5.9 (range 0.5-33) months.
Conclusions: Correlation of JAK2 MB and clinicopathological progression of MPNs is limited but several factors may provide minor predictive value.
|Mutation Burden (%) (Range)||WBC (k/uL)||Plt (k/uL)||BM Fibrosis (%) (n=26)||BM Cellularity (%) (n=26)||Vascular events (%)||Splenomegaly (%)|
|Overall (n=36)||31.19 (1.37-99.0)||13.02||473.2||42.3||67.2||58.3||41.7|
|ET (n=17)||18.53 (1.37-60.0)||10.62||652.3||36||68.4||61||38.9|
|PV (n=11)||44.61 (7.3-78.1)||14.81||357.4||25||81.6||81.8||54.5|
|MF (n=4)||69.54 (38.9-99.0)||24.13||140.5||100||60.0||0||0|