Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)

Abstract

Mutations of JAK2V617F, CALR, and MPL genes confirm the diagnosis of myeloproliferative neoplasm (MPN). This study aims to determine the genetic profile of JAK2V617F, CALR exon 9 Type 1 (52 bp deletion) and Type 2 (5 bp insertion), and MPL W515 L/K genes among Malaysian patients and correlate these mutations with clinical and hematologic parameters in MPN. Mutations of JAK2V617F, CALR, and MPL were analyzed in 159 Malaysian patients using allele-specific polymerase chain reaction, including 76 polycythemia vera (PV), 41 essential thrombocythemia (ET), and 42 primary myelofibrosis (PMF) mutations, and the demographics of the patients were retrieved. The result showed that 73.6% JAK2V617F, 5.66% CALR, and 27.7% were triple-negative mutations. No MPL W515L/K mutation was detected. In ET and PMF, the predominance type was the CALR Type 1 mutation. In JAK2V617F mutant patients, serum LDH was significantly higher in PMF compared to PV and ET. PV has a higher risk of evolving to post PV myelofibrosis compared to ET. A thrombotic event at initial diagnosis of 40.9% was high compared to global incidence. Only one PMF patient had a CALR mutation that transformed to acute myeloid leukemia. JAK2V617F and CALR mutations play an important role in diagnostics. Hence, every patient suspected of having a myeloproliferative neoplasm should be screened for these mutations.

The Impact of JAK2 V617F, CALR, and MPL Mutations as Molecular Diagnostic Markers of Myeloproliferative Neoplasms in Kurdish Patients. A Single-center Experience

“…Examining the demographic and clinical characteristics of PV patients showed that this average age, hemoglobin, HCT%, Leukocyte, and Platelet Count were higher than in the study conducted by RH Zulkeflee et al (33) and there was no significant difference between these patients, while in the mentioned study, there was a significant difference between WBC and Platelet Count.…”

Molecular Screening of Exon 12 of Janus Kinase 2, Exon 9 of Calreticulin Genes in Polycythemia Vera Patients with Unmutated Janus Kinase 2 V617F

“…ET and PMF patients that lack JAK2 V617F harbor CALR mutations 7.3 %-21.9 %, 5.3 %-30 %, respectively, whereas in all cases of PV had nonmutated CALR aberrations [16][17][18][19][20] . Type 1, 52 bp deletions were of most prevalence in ET [16,18,19,[21][22][23] , in contrast others reported type 2, 5 bp insertions [17] . Other than two major types, minor CALR variations were found in ET but not in PMF [16,19] and not observed in ET and PMF [18] but incidence were similar [17] .…”

“…According to the majority of studies, the frequency of JAK2 V617F mutation in negative-Breakpoint Cluster Region protein-Proto-Oncogene ABL (BCR-ABL) Philadelphia MPNs represented 75 %-95 % in PV, 60 %-73 % in ET and 45 %-63 % in MPF [16][17][18][19][20] , whereas the incidence of JAK2 exon 12 lesion is 4.5 %-5.76 % with wild JAK2 V617F PV of patients [17,21] . ET and PMF patients that lack JAK2 V617F harbor CALR mutations 7.3 %-21.9 %, 5.3 %-30 %, respectively, whereas in all cases of PV had nonmutated CALR aberrations [16][17][18][19][20] . Type 1, 52 bp deletions were of most prevalence in ET [16,18,19,[21][22][23] , in contrast others reported type 2, 5 bp insertions [17] .…”

“…Type 1, 52 bp deletions were of most prevalence in ET [16,18,19,[21][22][23] , in contrast others reported type 2, 5 bp insertions [17] . Other than two major types, minor CALR variations were found in ET but not in PMF [16,19] and not observed in ET and PMF [18] but incidence were similar [17] . The previous studies for PV individuals did not agree with our investigation.…”

Effects of calreticulin mutations on cell transformation and immunity

“… 3 , 4 While the most common JAK2 V617F mutation is found in around 95% of PV patients and 60% of ET and MF patients, about 15%–25% of ET and 25%–36% of MF patients carry CALR mutations, and 4%–9% of ET and MF patients carry MPL mutations. 3 , 4 , 5 , 6 …”