High Incidence of Myeloproliferative Disorders in Ashkenazi Jews in Northern Israel

Chaiter, Yoram; Brenner, Baruch; Aghai, E; Tatarsky, Ilana

doi:10.3109/10428199209053630

Cited by 58 publications

(40 citation statements)

References 11 publications

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“…46 In sporadic cases, the JAK2 46/1 haplotype has been associated with the acquisition of JAK2V617F mutation. 48,49 A high incidence of PV among Ashkenazi Jewish descent has been described, 50 but there are no clues as to genetic background.…”

Section: Evolving Concepts In Understanding Predisposition To Polycytmentioning

confidence: 99%

From leeches to personalized medicine: evolving concepts in the management of polycythemia vera

Vannucchi

2016

Haematologica

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© Ferrata Storti Foundationing to the level of knowledge we have now. Table 1 lists some of these landmark studies; due to space constraints, I will not be able to address all of them in detail. Evolving concepts in diagnosis Making a diagnosis of polycythemia veraThe World Health Organization (WHO) recently released a revised classification of MPN in which important changes to the 2008 version were introduced (Table 2). 8 In the 2008 version, the most compelling innovation had been the introduction of JAK2V617F and "similar" mutations (involving JAK2 exon 12 in 3%-4% of patients) as major diagnostic criteria.3-6 Although JAK2V617F mutation is associated with PV in more than 95% of cases, it does not represent a clear diagnosis since it is found also in 50%-60% of ET and PMF. However, the use of JAK2V617F as a marker of clonal myeloproliferation greatly facilitates the distinction of PV from reactive or congenital erythrocytosis.Considering that isotope-based assays for measuring red cell mass (RCM) and plasma volume are not routinely available even in most tertiary centers, the 2008 WHO classification listed a hemoglobin level more than 185 g/L and 165 g/L in men and women, respectively, as a strong surrogate marker of absolute increase of RCM. Since some PV patients do not fulfill such high levels, other criteria were added to facilitate diagnosis, including: 1) hemoglobin or hematocrit level that is more than 99 th percentile of reference range for age, sex, or altitude of residence; 2) an RCM that is more than 25% above mean normal predicted value;3) a hemoglobin level more than 170 g/L and 150 g/L in men and women, associated with a sustained increase of 20 g/L from baseline not attributable to correction of iron deficiency. According to the pragmatic British standards, hematocrit more than 52% in males and more than 48% in females, or an RCM more than 25% above predicted value, are sufficient to establish a diagnosis of PV if JAK2 mutation is present. 9 However, a reassessment of how far the WHO criteria can be applied in a real-life setting raised the issue of JAK2V617F mutated patients with only a borderline increase in hemoglobin. It was shown that BM morphology, according to WHO guidelines, accurately reflected a condition of increased RCM, since all patients with increased RCM also had a BM morphology consistent with PV.

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Section: Evolving Concepts In Understanding Predisposition To Polycytmentioning

confidence: 99%

From leeches to personalized medicine: evolving concepts in the management of polycythemia vera

Vannucchi

2016

Haematologica

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“…MMM has also been described in children where it seems to have a more benign course (6). Disease incidence is estimated from 0.5 to 1.5 per 100,000 population per year although the incidence may be higher in Ashkenazi Jews (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Myelofibrosis with Myeloid Metaplasia: New Developments in Pathogenesis and Treatment

2004

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Myeloid metaplasia with myelofibrosis (MMM) is a chronic myeloproliferative disorder (CMPD) characterized by progressive anemia, massive splenomegaly, both hepatosplenic and non-hepatosplenic extramedullary hematopoiesis (EMH), a leukoerythroblastic blood smear, circulating progenitor cells, and marked bone marrow stromal reaction including collagen fibrosis, osteosclerosis and angiogenesis. The overall median survival is 5 years although it might range from 2 to 15 years depending on the presence or absence of clinically defined prognostic factors. Death is often due to leukemic transformation, portal hypertension or infection. In addition to shortened survival, quality of life is often affected by frequent red blood cell transfusions, profound constitutional symptoms, and cachexia. Drug therapy and autologous hematopoietic stem cell transplantation (HSCT) are of only palliative value and have not been shown to improve survival. The role of allogeneic HSCT, both myeloablative and non-myeloablative, is actively being investigated. Both splenectomy and radiation therapy have defined therapeutic roles to control EMH-associated symptoms. Analysis of the molecular biology of the disease is underway with the aid of animal models leading to the identification of novel therapeutic targets. Among the novel agents tested, thalidomide seems the most promising although newer agents are on the horizon.

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“…Although the disorder was first described in 1879 by Heuck [2], it was not until 1951, following Damshek’s [3]seminal paper, that idiopathic myelofibrosis was regarded as one of the chronic myeloproliferative disorders. It is an uncommon disease, with a reported annual incidence of around 0.4 per 100,000 population [4, 5], with the highest rates being documented among Ashkenazi Jews in northern Israel [6]. The disease’s aetiology remains largely unknown, although environmental factors may be relevant in a minority of patients, in view of the reported links with radiation [7, 8], as well as benzene and toluene exposure [9, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic and Molecular Genetic Aspects of Idiopathic Myelofibrosis

Reilly

2002

Acta Haematol

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Idiopathic myelofibrosis is a chronic myeloproliferative disorder in which the characteristic fibroblast proliferation is thought to be a secondary phenomenon resulting from the inappropriate release of megakaryocyte- and/or monocyte-derived growth factors, including PDGF, TGF-β, bFGF and calmodulin. In contrast, the haematopoietic cells are clonal, although the underlying pathogenetic mechanisms remain essentially unknown. Cytogenetic studies have highlighted that 13q–, 20q–, +8 and abnormalities of chromosomes 1, 7 and 9 constitute more than 80% of the chromosomal changes. A third of idiopathic myelofibrosis cases have abnormal karyotypes at diagnosis, a figure that increases if follow-up analyses are performed. Evolution to more complex karyotypes may accompany clinical progression, with abnormalities increasing to around 90% following acute leukaemic transformation. Cytogenetic abnormalities have been associated with prognosis and to a lack of treatment response to androgens. Oncogene mutations are rare and include point mutations in N-RAS, c-KIT and TP53.

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High Incidence of Myeloproliferative Disorders in Ashkenazi Jews in Northern Israel

Cited by 58 publications

References 11 publications

From leeches to personalized medicine: evolving concepts in the management of polycythemia vera

From leeches to personalized medicine: evolving concepts in the management of polycythemia vera

Myelofibrosis with Myeloid Metaplasia: New Developments in Pathogenesis and Treatment

Cytogenetic and Molecular Genetic Aspects of Idiopathic Myelofibrosis

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