P1012: characterizing jak2 mutated and unmutated erythrocytosis: a clinical and genetic comparison

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: Erythrocytosis refers to increase in hemoglobin/hematocrit and hereditary or acquired causes exist. Clonal myeloproliferative neoplasm characterized by erythrocytosis is called polycythemia vera and is strongly associated with JAK2 mutations. Targeted sequencing for myeloproliferative neoplasm or hereditary erythrocytosis can be performed easily but the diagnostic algorithm and approach is different for acquired or congenital causes. Aims: We aimed to characterize JAK2 unmutated erythrocytosis from JAK2 mutated erythrocytosis. Methods: 162 patients referred due to erythrocytosis from 2019 through 2022, who had undergone either JAK2 sanger sequencing or 38 gene targeted myeloid panel sequencing, were included. Clinical characteristics and laboratory findings were compared between JAK2 mutated and unmutated erythrocytosis. Among JAK2 unmutated erythrocytosis additional gene panel (EGLN1, HIF1A, EPAS1, VHL, EPO, EPOR, JAK2, SH2B3, CBL, BPGM, EPB41, EPB42, PIEZO1, PKLR, RHAG, NF1, SLC4A1) to identify genetic variants associated with hereditary erythrocytosis was performed in 19 patients. Results: Among 162 patients with erythrocytosis, 27.8% (n = 45) showed JAK2 mutations and the remaining (72.2%) were negative for JAK2 mutations (n = 117). JAK2 unmutated patients showed lower age and higher male predominance (P < 0.001). For the complete blood cell parameters, red blood cell count, hematocrit, white blood cell count, absolute neutrophil count and platelet count were significantly lower in JAK2 unmutated than JAK2 mutated erythrocytosis (P < 0.001). On the other hand, mean corpuscular volume, mean corpuscular hematocrit and mean corpuscular hemoglobin concentration were higher in JAK2 unmutated erythrocytosis (P < 0.001). Other laboratory findings including erythropoietin (EPO), ferritin, iron, were significantly higher in JAK2 unmutated erythrocytosis (P < 0.001) with none of the JAK2 unmutated patients showed EPO level under normal range. The percentage of abnormal karyotype and the number of additional mutations detected were not different in the two groups (P = 0.155, 0.617, respectively). Among 19 JAK2 unmutated patients who undergone gene testing for hereditary erythrocytosis, five (26.3%) patients had at least one reportable variant and pathogenic variant was detected in one patient in NF1, and variants of undetermined significances in EPAS1, RHAG, VHL and PIEZO1. Summary/Conclusion:JAK2 unmutated erythrocytosis patients had significantly different CBC parameters and laboratory findings compared to JAK2 mutated patients. Combining clinical characteristics and lab findings, selection of targeted gene panel testing for acquired or hereditary erythrocytosis may be performed. The detection of variants with hereditary erythrocytosis panel is limited and causes of many of the JAK2 unmutated erythrocytosis is not well deciphered only with the germline panel testing requiring further investigation. Keywords: Erythrocytosis