Familial Polycythemia Caused by a Novel Mutation in the Beta Globin Gene: Essential Role of P50 in Evaluation of Familial Polycythemia

Agarwal, Neeraj; Mojica-Henshaw, Mariluz P.; Simmons, Elizabeth. D.; Hussey, Dottie; Ou, Ching Nan; Prchal, Josef T.

doi:10.7150/ijms.4.232

Cited by 27 publications

(22 citation statements)

References 15 publications

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“…In those patients with a low value for P50 sequencing of the globin gene to establish and resistance to the glucocorticoids in particular has been shown to be related to an unfavorable event free survival. 3,4 Since the glucocorticoids prednisolone and dexamethasone play a crucial role in essentially all therapy protocols, the development of strategies to reverse resistance to these agents is important to improve ALL treatment efficacy. Recently, we have demonstrated that glucocorticoid resistance in pediatric ALL is associated with increased glucose metabolism, and that inhibition of glycolysis sensitizes prednisolone-resistant ALL cells to glucocorticoids.…”

mentioning

confidence: 99%

Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis

Percy¹,

Butt²,

Crotty³

et al. 2009

Haematologica

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confidence: 99%

Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis

Percy¹,

Butt²,

Crotty³

et al. 2009

Haematologica

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“…According to these findings, we strongly suspected the presence of a Hb variant with a high oxygen affinity or 2,3-BPGM deficiency (1)(2)(3)(4)(5).…”

Section: Case Reportmentioning

confidence: 85%

“…Meanwhile, algorithms for a definitive diagnosis are being established for congenital erythrocytosis, for which the number of cases is also small (1)(2)(3)(4). Among these algorithms, a P50 measurement using an apparatus to analyse blood gases is a fast and simple test with proven efficacy that reflects a shift in the ODC (1)(2)(3)(4)(5)24). In addition to a family history, a low P50 level in the present patient was observed using the automated blood gas analyser, which strongly suggested the presence of a high oxygen affinity haemoglobinopathy.…”

Section: Discussionmentioning

confidence: 99%

“…Some previous cases with Hb Bethesda also showed a low P50 value (<13 mmHg), although the value was measured by in vitro experiments of the ODC (8-10, 12, 13). Hence, for the patients in whom acquired erythrocytosis is diagnosed by exclusion, a P50 measurement is recommended (1)(2)(3)(4)(5)24). Despite this, patients suspected of having congenital erythrocytosis, in whom a definitive diagnosis is possible, account for approximately 30% of all cases (3,4,13).…”

Section: Discussionmentioning

confidence: 99%

“…The P50 measurements served as an important step during the course of the definitive diagnosis (1)(2)(3)(4)(5). Many patients with erythrocytosis, whom we encounter in daily medical practice, may have hidden haemoglobinopathies, such as Hb Bethesda, highlighting the importance of differentiating various types of congenital erythrocytosis (1-5).…”

Section: Discussionmentioning

confidence: 99%

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A Japanese Family with Congenital Erythrocytosis Caused by Haemoglobin Bethesda

Tamura

Gima

et al. 2015

Intern. Med.

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We herein present a case of congenital erythrocytosis caused by haemoglobin (Hb) Bethesda in a Japanese family. A 55-year-old asymptomatic man was referred to our hospital for the investigation of erythrocytosis, which was present in other members of his family. The patient's serum erythropoietin level was normal, and the JAK2 V617F mutation was not detected. His P50 value was mildly decreased, thus we suspected the presence of an Hb variant with a high oxygen affinity. The high-performance liquid chromatography analysis showed an abnormal Hb, and by direct sequencing we identified the Hb Bethesda variant in this patient. For the differential diagnosis, we recommend the estimation of the P50 value as a practical and useful test.

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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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Familial Polycythemia Caused by a Novel Mutation in the Beta Globin Gene: Essential Role of P50 in Evaluation of Familial Polycythemia

Cited by 27 publications

References 15 publications

Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis

Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis

A Japanese Family with Congenital Erythrocytosis Caused by Haemoglobin Bethesda

JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management

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