Impact of JAK2 V617F Mutation on Hemogram Variation in Patients with Non-Reactive Elevated Platelet Counts

Abstract

BackgroundNon-reactive platelet counts elevation occurs mainly in myeloproliferative disorders (MPDs), which have been reported to be closely associated with JAK2 V617F mutation. Complete blood cell count (CBC) is essential in diagnosis of MPDs, however, the impact of JAK2 V617F mutation on the patients’ hemogram variation remains not clear.MethodsJAK2 V617F mutation was detected by allele specific real-time quantitative fluorescence PCR (AS-qPCR).ResultsOf the 402 non-reactive platelet elevating patients, JAK2 V617F mutation was detected in 222 (55.2%) patients. RBC counts, WBC counts, platelet-large contrast ratio (P-LCR), platelet distribution width (PDW) and mean platelet volume (MPV) were much higher in JAK2 V617F mutated patients, except platelet counts. In addition, when the patients were classified into subgroups by blood cell counts, it was found that JAK2 V617F mutation rate increased progressively with the increase of RBC counts and WBC counts, other than platelet counts. Furthermore, trilineage hyperplasia group showed highest JAK2 V617F mutation rate (93.26%), followed by the bilineage hyperplasia groups. Lastly, JAK2 V617F mutant allele burden was found much higher in polycythemia vera (PV) patients [median(P25–P75): 45.02%(35.12%–54.22%)] than in essential thrombocythemia (ET) patients [median(P25–P75): 28.23%(17.77%–41.66%)], and that it increased with WBC counts (r = 0.393, p = 0.000) and RBC counts(r = 0.215, p = 0.001), other than platelet counts (r = −0.051, p = 0.452). Further analysis revealed that in ET patients, JAK2 V617F mutant allele burden correlated with WBC counts and platelet counts positively, other than RBC counts, while in PV patients, it correlated with WBC counts and RBC counts positively, but not platelet counts.ConclusionsJAK2 V617F mutation occurs frequently in patients with non-reactive elevated platelet counts. The presence of JAK2 V617F mutation has great impact on hemogram variation, including RBC counts, WBC counts, platelet parameters and lineage hyperplasia, but not on platelet counts. Besides, JAK2 V617F mutant allele burden affects the blood cell proliferation pattern.

Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis

“…Campbell et al [13] [15]. Several studies have shown that the prevalence of the JAK2 V617F mutation in ET is ranging approximately from 23 to 69 % [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In the present study, the frequency of JAK2 V617F mutation positive was 46 % in ET, which is consistent with the studies in the literatures.…”

“…Campbell et al [13] [15]. Several studies have shown that the prevalence of the JAK2 V617F mutation in ET is ranging approximately from 23 to 69 % [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

“…Similarly we have found that MPV is significantly higher, PDW is higher with no significance in mutated patients. Since large platelet represents new and immature platelet, particular studies indicated that JAK2 V617F mutation was significantly associated with increase of immature platelets [15,29]. It was supposed that JAK2 V617F may promote thrombopoiesis and caused to hyperplasia of megakaryocytic progenitor cells in the bone marrow [30].…”

Normal platelet counts mask abnormal thrombopoiesis in patients with chronic myeloid leukemia

“…However, regulation of this process may be disrupted in certain diseases, particularly in neoplasms with a clonal origin (12,(18)(19)(20). It was hypothesized that dysmegakaryocytes reflect disorders of megakaryocyte development and result in dysregulated platelet production, as indicated by higher MPV, P-LCR and PDW values in patients with CML than in healthy controls.…”

Relationship betweenJAK2V617Fmutation, allele burden and coagulation function in Ph-negative myeloproliferative neoplasms

“…Recently, the discovery of the JAK2V617F [4], CALR [5], and MPL [6] mutation provided new genetic markers and changed the diagnostic criteria of Ph-negative MPNs. The JAK2V617F mutation, resulting from a single G to T transversion occurs at base position 1849 in exon 14 of the JAK2 gene and leads to a valine to phenylalanine substitution at codon 617, which consequently increases the tyrosine kinase activity, thus resulting in clonal proliferation of one or several myeloid lineages [7] In patients with Ph-negative MPN, cases with a higher JAK2V617F allele burden were thought to have higher hematologic parameters, such as white blood cell counts, hemoglobin values, and platelet counts [8][9][10][11][12]. In addition, accumulating studies about the association between JAK2V617F mutation and vascular events in Ph-negative MPN patients have been reported [13,14] and a higher risk of suffering with vascular events was investigated in patients with JAK2V617F mutation [15,16].…”