The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis

Smalberg, Jasper H.; Koehler, Edith M.; Murad, Sarwa Darwish; Plessier, Aurélie; Seijó, Susana; Trebicka, Jonel; Primignani, Massimo; Maat, Moniek P.M. de; García-Pagán, Juan Carlos; Valla, Dominique; Janssen, Harry L.A.; Leebeek, Frank W.G.

doi:10.1182/blood-2010-11-319087

Cited by 44 publications

(43 citation statements)

References 24 publications

(40 reference statements)

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“…A recent study in Chinese MPNs revealed 46/1 is associated with platelet count in PV and PMF, and raised haemoglobin and haematocrit in ET [Wang et al 2013]. A significant excess of 46/1 alleles has been reported in JAK2 V617F-positive splanchnic vein thrombosis (SVT) patients, and the presence of 46/1 has been correlated with increased erythropoiesis in JAK2 V617F negative cases with SVT [Smalberg et al 2011]. It might also be expected that 46/1 could influence blood counts in normal individuals.…”

Section: Familial Mpnmentioning

confidence: 99%

Inherited predisposition to myeloproliferative neoplasms

Jones

Cross

2013

Therapeutic Advances in Hematology

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Myeloproliferative neoplasms (MPNs) are haematological disorders characterized by an overproduction of mature myeloid cells with a tendency to transform to acute myeloid leukaemia. Clonal proliferation of myeloid progenitor cells is driven by somatically acquired mutations, most notably JAK2 V617F, but there are important features relating to pathogenesis and phenotypic diversity that cannot be explained by acquired mutations alone. In this review we consider what is currently known about the role that inherited factors play in the development and biology of both sporadic and familial forms of MPN. Although most MPN cases appear to be sporadic, familial predisposition has been recognized for many years in a subset of cases and epidemiological studies have indicated the presence of common susceptibility alleles. Currently the JAK2 46/1 haplotype (also referred to as 'GGCC') is the strongest known predisposition factor for sporadic MPNs carrying a JAK2 V617F mutation, explaining a large proportion of the heritability of this disorder. Less is known about what genetic variants predispose to MPNs that lack JAK2 V617F, but there have been recent reports of interesting associations in biologically plausible candidates, and more loci are set to emerge with the application of systematic genome-wide association methodologies. Several highly penetrant predisposition variants that affect erythropoietin signalling, thrombopoietin signalling or oxygen sensing have been characterized in families with nonclonal hereditary erythrocytosis or thrombocytosis, but much less is known about familial predisposition to true clonal MPN. The heterogeneous pattern of inheritance and presumed genetic heterogeneity in these families makes analysis difficult, but whole exome or genome sequencing should provide novel insights into these elusive disorders.

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Section: Familial Mpnmentioning

confidence: 99%

Inherited predisposition to myeloproliferative neoplasms

Jones

Cross

2013

Therapeutic Advances in Hematology

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“…5,6 An increased frequency of the 46/1 haplotype in patients with splanchnic vein thrombosis has also been reported but these findings remain controversial. 7,8 The 46/1 haplotype has been studied in chronic myelogenous leukemia and in chronic myelomonocytic leukemia; no significant increase in frequency was noted (Table 1). Last year Andrikovics et al reported that patients with acute myeloid leukemia (AML) with the 46/1 haplotype had a higher frequency of normal karyotype (NK).…”

mentioning

confidence: 99%

The JAK2 46/1 haplotype: a marker of inappropriate myelomonocytic response to cytokine stimulation, leading to increased risk of inflammation, myeloid neoplasm, and impaired defense against infection?

Hermouet¹,

Vilaine²

2011

Haematologica

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“…In China, MOVC is the most common type of BCS whose development is characterized by membranous formation above the junction of the inferior vena cava and hepatic veins with vascular endothelial tissues on both surfaces of the membrane. In recent years, etiological studies of BCS have focused on genetic thrombosis caused by the mutation of genes such as G1691A (clotting factor V gene; the mutation is also known as the FVLeiden mutation) (Slusher, 2010), G20210A (prothrombin gene; FIIG20210A) (Wlazłowski et al, 2011), JAK2-V617F (Tondeur et al, 2010;Smira et al, 2010;Smalberg et al, 2011), and so on. These causes are closely related to hepatic vein thrombosis and hepatic venous occlusion Table 2.…”

Section: Discussionmentioning

confidence: 99%