The likelihood of a JAK2 mutation was highest among patients presenting with polycythemia vera (PV) compared with those who had either essential thrombocythemia (ET) or primary myelofibrosis (PMF), although patients with the former disease did not show evidence of alterations in either MPL or CALR, according to results of a meta-analysis published in BMC Cancer.

The 3 Philadelphia chromosome-negative (ie, BCR-ABL1-negative) chronic myeloproliferative neoplasms (MPNs), PV, ET, and PMF are characterized by excessive production of mature erythroid, megakaryocytic, and granulocytic stem cells, respectively. Vascular complications, including both thrombosis and bleeding, are common in these diseases, and patients with ET are at increased risk of transformation to secondary PMF. In addition, all 3 of these diseases can potentially progress to acute myeloid leukemia. Hence, accurate and discriminating diagnostic criteria are critically important in this setting.

The aim of this study was to perform a systematic review of studies published between 2003 and 2018 of patients with PV, ET, and PMF, as well as a meta-analysis of those studies that reported on the frequencies of driver alterations in the JAK2, MPL, and/or CALR genes of patients with these diseases.

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Fifty-two analytical studies met criteria for inclusion in the systematic review, with the meta-analysis based on a subset of 18 of those studies. Of the 27,078 patients included in the 52 studies, 12.9% (n=3488 patients) had PV, 19.6% (n=5300 patients) had ET, and 7.2% (n=1954 patients) had PMF; in addition, 4.0% of patients were healthy controls, and the remaining patients were classified as having other diseases.

Thus, of the patients in these studies with MPNs, 49.34%, 32.47%, and 18.19% were classified as having ET, PV, and PMF, respectively.

“This distribution correlates with the incidents reported worldwide for this group of neoplasms,” the study authors noted.

A high degree of heterogeneity was reported across the included studies with respect to their main focus (ie, clinical characteristics, genomic characterization, and associated cellular and metabolic processes), as well as the methods used to elucidate the 3 targeted molecular alterations, although “the main interest has been the frequency and clinical correlation of these 3 mutations,” they noted.

Across studies, the observed ranges of frequencies of JAK2 V617F alterations were as follows: 46.7% to 100% for PV, 31.3% to 72.1% for ET, and 25.0% to 85.7% for PMF. With respect to MPL, mutational frequencies were 0% for PV, and ranges of 0.9% to 12.5% for ET and 0 to 17.1% for PMF. Finally, CALR mutations were detected in 0% of patients with PV, and frequencies of CALR alterations ranged from 12.6% to 50% for ET, and 0% to 100% for PMF.

Results of the meta-analysis focused on these molecular alterations showed that patients with PV are 3 times more likely than those with ET and 4 times more likely than those with PMF to present with disease characterized by a JAK2 V617F alteration. Furthermore, MPL alterations were found to be 3 times more likely in patients with PMF compared with those with ET, and similar frequencies of CALRalterations were observed in patients with PMF and ET.

“Given the specificity and reported high frequencies of the JAK2 V617F, MPLand CALRmutations in this group of neoplasms, the diagnosis of these diseases should not be made on clinical and hematological characteristics alone but should include genetic screening of patients,” the study authors concluded.

Reference 1, Mejía-Ochoa M, Acevedo Toro PA, Cardona-Arias JA. Systematization of analytical studies of polycythemia vera, essential thrombocythemia and primary myelofibrosis, and a meta-analysis of the frequency of JAK2, CALR and MPL mutations: 2000-2018.BMC Cancer. 2019;19(1):590.