Characteristics of JAK2 unmutated erythrocytosis: Distinctive traits between polycythemia vera and non-polycythemia vera patients

Ernest, Vincent; Abbou, Norman; Tichadou, Antoine; Arcani, Robin; Venton, Geoffroy

doi:10.1016/j.ejim.2022.09.004

Cited by 3 publications

(3 citation statements)

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“…The clinical phenotype of secondary erythrocytosis differs from PV; patients with secondary erythrocytosis are more likely to be males, display isolated erythrocytosis with lower white and platelet counts, higher Epo levels, lower lactate dehydrogenase levels, without palpable splenomegaly. 14,47,48 Most studies have observed a lower incidence of thrombosis with secondary erythrocytosis in comparison to PV, [47][48][49] while two retrospective studies have suggested a similar thrombotic risk as in PV. 14,50 It is to be noted that the latter studies did not account for the causal diversity of secondary erythrocytosis.…”

Section: Diagnosismentioning

confidence: 99%

“…As a next step in the evaluation of erythrocytosis, a comprehensive medical assessment including careful review of prior blood counts, medications, and family history is recommended. The clinical phenotype of secondary erythrocytosis differs from PV; patients with secondary erythrocytosis are more likely to be males, display isolated erythrocytosis with lower white and platelet counts, higher Epo levels, lower lactate dehydrogenase levels, without palpable splenomegaly 14,47,48 . Most studies have observed a lower incidence of thrombosis with secondary erythrocytosis in comparison to PV, 47–49 while two retrospective studies have suggested a similar thrombotic risk as in PV 14,50 .…”

Section: Diagnosismentioning

confidence: 99%

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JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management

2023

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Disease Overview JAK2 unmutated or non‐polycythemia vera (PV) erythrocytosis encompasses a heterogenous spectrum of hereditary and acquired entities. Diagnosis Foremost in the evaluation of erythrocytosis is the exclusion of PV through JAK2 (inclusive of exons 12–15) mutation screening. Initial assessment should also include gathering of previous records on hematocrit (Hct) and hemoglobin (Hgb) levels, in order to streamline the diagnostic process by first distinguishing longstanding from acquired erythrocytosis; subsequent subcategorization is facilitated by serum erythropoietin (Epo) measurement, germline mutation screening, and review of historical data, including comorbid conditions and medication list. Hereditary erythrocytosis constitutes the main culprit in the context of longstanding erythrocytosis, especially when associated with a positive family history. In this regard, a subnormal serum Epo level suggests EPO receptor mutation. Otherwise, considerations include those associated with decreased (high oxygen affinity Hgb variants, 2,3‐bisphosphoglycerate deficiency, PIEZO1 mutations, methemoglobinemia) or normal oxygen tension at 50% Hgb saturation (P50). The latter include germline oxygen sensing pathway (HIF2A–PHD2–VHL) and other rare mutations. Acquired erythrocytosis commonly results from central (e.g., cardiopulmonary disease, high‐altitude habitat) or peripheral (e.g., renal artery stenosis) hypoxia. Other noteworthy conditions associated with acquired erythrocytosis include Epo‐producing tumors (e.g., renal cell carcinoma, cerebral hemangioblastoma) and drugs (e.g., testosterone, erythropoiesis stimulating agents, sodium‐glucose cotransporter‐2 inhibitors). Idiopathic erythrocytosis is an ill‐defined terminology that presumes the existence of an increased Hgb/Hct level without an identifiable etiology. Such classification often lacks accounting for normal outliers and is marred by truncated diagnostic evaluation. Management Current consensus treatment guidelines are not supported by hard evidence and their value is further undermined by limited phenotypic characterization and unfounded concerns for thrombosis. We are of the opinion that cytoreductive therapy and indiscriminate use of phlebotomy should be avoided in the treatment of non‐clonal erythrocytosis. However, it is reasonable to consider therapeutic phlebotomy if one were to demonstrate value in symptom control, with frequency determined by symptoms rather than Hct level. In addition, cardiovascular risk optimization and low dose aspirin is often advised. Future Directions Advances in molecular hematology might result in better characterization of “idiopathic erythrocytosis” and expansion of the repertoire for germline mutations in hereditary erythrocytosis. Prospective controlled studies are needed to clarify potential pathology from JAK2 unmutated erythrocytosis, as well as to document the therapeutic value of phlebotomy.

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Section: Diagnosismentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management

2023

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“…Secondary erythrocytosis is attributed to various causes, hypoxia, high altitude, smoking, obstructive sleep apnea, and medications such as androgen and sodium-glucose cotransporter 2 (SGLT2) inhibitors [ 4 ], and requires thorough evaluation to identify the causes. Nonetheless, many patients remain undiagnosed and do not undergo further investigations following the exclusion of PV [ 5 ], and symptoms are managed through phlebotomy. Recent advances in genetic testing have increasingly identified patients with germline mutations in genes, including EPAS1 , EGLN1 , VHL , EPO , EPOR , PIEZO1 , and BPGM .…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Approaches to Investigate JAK2-Unmutated Erythrocytosis Based on a Single Tertiary Center Experience

Lee,

Seo,

Kim

et al. 2024

Mol Diagn Ther

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Introduction Erythrocytosis is attributed to various clinical and molecular factors. Many cases of JAK2 -unmutated erythrocytosis remain undiagnosed. We investigated the characteristics and causes of JAK2 -unmutated erythrocytosis. Methods We assessed the clinical and laboratory results of patients with erythrocytosis without JAK2 mutations and performed targeted next-generation sequencing (NGS) panels for somatic and germline mutations. Results In total, 117 patients with JAK2 -unmutated erythrocytosis were included. The median hemoglobin and hematocrit levels were 17.9 g/dL and 53.4%, respectively. Erythropoietin levels were not below the reference range. Thrombotic events were reported in 17 patients (14.5%). Among JAK2 -unmutated patients, 44 had undergone targeted panel sequencing consisting of myeloid neoplasm-related genes, and 16 had one or more reportable variants in ASXL1 (5/44), TET2 , CALR , FLT3 , and SH2B3 (2/44). Additional testing for germline causes revealed eight variants in seven genes in eight patients, including NF1 , BPGM , EPAS1 , PIEZO1 , RHAG , SH2B3 , and VHL genes. One NF1 pathogenic, one BPGM likely pathogenic, and six variants of undetermined significance were detected. Conclusion Somatic and germline mutations were identified in 36.4% and 33.3 % of the JAK2 -unmutated group; most variants had unknown clinical significance. Not all genetic causes have been identified; comprehensive diagnostic approaches are crucial for identifying the cause of erythrocytosis.

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Can we use platelet-to-lymphocyte ratio (PLR) to differentiate JAK2-unmutated erythrocytosis from polycythemia vera?

Krečak¹,

Lucijanić²

2023

European Journal of Internal Medicine

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Characteristics of JAK2 unmutated erythrocytosis: Distinctive traits between polycythemia vera and non-polycythemia vera patients

Cited by 3 publications

References 10 publications

JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management

JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management

Diagnostic Approaches to Investigate JAK2-Unmutated Erythrocytosis Based on a Single Tertiary Center Experience

Can we use platelet-to-lymphocyte ratio (PLR) to differentiate JAK2-unmutated erythrocytosis from polycythemia vera?

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