İstanbul University İstanbul Medical Faculty, Department of Internal Medicine, Division of Hematology, İstanbul, Türkiye
University of Health Sciences Türkiye Bakırköy Dr. Sadi Konuk Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
Turk J Haematol. 2023 Aug 31;40(3):174-182. doi: 10.4274/tjh.galenos.2023.2023.0169. Epub 2023 Aug 16.
The impact of allele burden on clinical course in Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) is not clear. We analyzed the clinical impact of allele burden in a relatively large series of patients with Ph-negative MPNs and long-term follow-up.
A total of 228 patients with Ph-negative MPNs, including 118 with essential thrombocythemia (ET), 84 with primary myelofibrosis (PMF), and 26 with polycythemia vera (PV), were analyzed. The JAK2 MutaScreen assay was used to quantify allele burden in genomic DNA.
In PV cases, high allele burden was associated with a trend towards inferior overall survival. In ET, high allele burden was associated with lower hemoglobin and hematocrit levels, higher lactate dehydrogenase (LDH) levels, larger spleen size, and increased bleeding and mortality rates. In PMF, high allele burden was associated with higher leukocyte counts and larger spleen size. In the entire cohort, high allele burden was associated with higher leukocyte and lower platelet counts, higher LDH levels, larger spleen size, higher percentage of bleeding events, higher death rate, and inferior overall survival.
Our results suggest that high allele burdens are associated with more severe disease in PV and ET. In PMF, high allele burdens were associated with more pronounced myeloproliferative phenotypes. In Ph-negative MPNs, high allele burdens were associated with more aggressive phenotypes. Our data with a long follow-up period support the possibility of allele burden being used as a marker for predicting clinical phenotype in cases of Ph-negative MPNs.
等位基因负担对费城染色体阴性（Ph-阴性）骨髓增殖性肿瘤（MPN）临床病程的影响尚不清楚。我们分析了在相对较大系列的 Ph-阴性 MPN 患者和长期随访中，等位基因负担的临床影响。
共分析了 228 例 Ph-阴性 MPN 患者，包括 118 例特发性血小板增多症（ET）、84 例原发性骨髓纤维化（PMF）和 26 例真性红细胞增多症（PV）。使用 JAK2 MutaScreen 检测法定量分析基因组 DNA 中的等位基因负担。
在 PV 病例中，高等位基因负担与总生存趋势较差相关。在 ET 中，高等位基因负担与较低的血红蛋白和血细胞比容水平、较高的乳酸脱氢酶（LDH）水平、更大的脾脏大小以及更高的出血和死亡率相关。在 PMF 中，高等位基因负担与更高的白细胞计数和更大的脾脏大小相关。在整个队列中，高等位基因负担与更高的白细胞计数和较低的血小板计数、更高的 LDH 水平、更大的脾脏大小、更高的出血事件发生率、更高的死亡率和较差的总体生存率相关。
我们的结果表明，高等位基因负担与 PV 和 ET 中更严重的疾病相关。在 PMF 中，高等位基因负担与更明显的骨髓增殖表型相关。在 Ph-阴性 MPN 中，高等位基因负担与更具侵袭性的表型相关。我们的数据具有较长的随访期，支持等位基因负担可用作预测 Ph-阴性 MPN 病例临床表型的标志物的可能性。
