A higher <i>JAK2</i>V617F allele burden may be a risk factor for hemorrhagic events in younger patients with polycythemia vera
Creators: name: Furuya, Chiho
name: Hashimoto, Yoshinori
name: Morishita, Soji
name: Fukuda, Yasutaka
name: Inano, Tadaaki
name: Ochiai, Tomonori
name: Shirane, Shuichi
name: Edahiro, Yoko
name: Araki, Marito
name: Ando, Miki
name: Komatsu, Norio
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Science Policy
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV). We analyzed the characteristics of hemorrhagic events in 267 patients with PV. A median follow-up of 4.8 years revealed that 23 (8.6%) hemorrhagic events occurred. Significantly more hemorrhagic events occurred in younger patients aged below 60 years (n = 72) than in older patients aged 60 years or above (n = 191) (n = 12 [16.7%] vs. n = 11 [5.8%], respectively, <i>P</i> = 0.012). In univariate analysis among the younger patients, white blood cell (WBC) count ≥ 15 × 10<sup>9</sup>/L (hazard ratio [HR] = 7.746, 95% confidence interval [CI] 2.082-28.830, <i>P</i> = 0.002), palpable splenomegaly (HR = 5.629, 95% CI 1.193–26.550, <i>P</i> = 0.029), and <i>JAK2</i>V617F allele burden ≥ 80% (HR = 22.850, 95% CI 2.885–181.00, <i>P</i> = 0.003) were associated with an increased risk of hemorrhagic events. In multivariate analysis, <i>JAK2</i>V617F allele burden ≥ 80% (HR = 9.394, 95% CI 1.046–84.380, <i>P</i> = 0.046) was a significant risk factor. There is an increased risk of hemorrhagic events after diagnosis in younger PV patients with a high <i>JAK2</i>V617F allele burden, high WBC count or palpable splenomegaly. It is important to consider treatment options that aim to avoid hemorrhagic events by reducing the <i>JAK2</i>V617F allele burden in younger PV patients. Polycythemia vera (PV) is a subtype of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) that results in the overproduction of red blood cells (RBCs) due to persistent activation of the JAK2-STAT5 pathway caused by mutations in the Janus kinase 2 (<i>JAK2</i>) gene. Complications associated with elevated RBC counts include thrombosis, hemorrhage, and microvascular symptoms (such as headache and erythromelalgia) due to microcirculatory insufficiency, resulting in reduced quality of life. Hemorrhagic events are a rare but potentially fatal complication in patients with PV. However, specific risk factors for hemorrhagic events in PV remain to be elucidated. In this study, we sought to analyze the association between clinical characteristics and hemorrhagic events in 267 patients with PV in order to clarify the characteristics of these events. We found that patients with PV younger than 60 years, those with a high <i>JAK2</i>V617F allele burden (≥ 80%) (hazard ratio [HR] = 22.850, 95% confidence interval [CI] 2.885–181.000, <i>P</i> = 0.003), a higher white blood cell (WBC) count (WBC ≥ 15 × 10<sup>9</sup>/L) (HR = 7.746, 95% CI 2.082–28.830, <i>P</i> = 0.002)or palpable splenomegaly (HR = 5.629, 95% CI 1.193–26.550, <i>P</i> = 0.029) at diagnosis may be at an increased risk of hemorrhagic events after diagnosis. Based on these observations, it would be important to consider the potential benefits of drug therapies aimed at reducing the <i>JAK2</i>V617F allele burden in younger patients with PV. Here, we suggest that these therapies may help to reduce the incidence of hemorrhagic events.