The <i>JAK2</i> 46/1 (<i>GGCC</i>) MPN‐predisposing haplotype: A risky haplotype, after all

Vannucchi, Alessandro M.; Guglielmelli, Paola

doi:10.1002/ajh.25367

Cited by 5 publications

(8 citation statements)

References 28 publications

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“…This is consistent with the fact that disorders sharing the same somatic driver mutations are nevertheless typified by an extremely heterogenous presentation and behavior. The increasingly widespread use of novel techniques such as Next-Generation Sequencing during the routine diagnostic work-up of MPN patients will allow us to detect prognostically relevant SNPs and potentially include them in a personalized risk stratification, as envisioned, for example, for the JAK2 46/1 haplotype [81].…”

Section: Discussionmentioning

confidence: 99%

The Genetic Makeup of Myeloproliferative Neoplasms: Role of Germline Variants in Defining Disease Risk, Phenotypic Diversity and Outcome

Masselli

Pozzi

Carubbi

et al. 2021

Cells

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Myeloproliferative neoplasms are hematologic malignancies typified by a substantial heritable component. Germline variants may affect the risk of developing a MPN, as documented by GWAS studies on large patient cohorts. In addition, once the MPN occurred, inherited host genetic factors can be responsible for tuning the disease phenotypic presentation, outcome, and response to therapy. This review covered the polymorphisms that have been variably associated to MPNs, discussing them in the functional perspective of the biological pathways involved. Finally, we reviewed host genetic determinants of clonal hematopoiesis, a pre-malignant state that may anticipate overt hematologic neoplasms including MPNs.

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Section: Discussionmentioning

confidence: 99%

The Genetic Makeup of Myeloproliferative Neoplasms: Role of Germline Variants in Defining Disease Risk, Phenotypic Diversity and Outcome

Masselli

Pozzi

Carubbi

et al. 2021

Cells

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“…As described, JAK2V617F leads to clonal proliferation in MPNs; however, it is not clear which factors influence the development, severity and phenotype of the disease [ 66 ]. The latter is possibly related to individual characteristics (sex, associated inflammatory disease), and genetic abnormalities (driver genes, pathogenic genetic variants and other chromosomal aberrations) [ 71 ]. Different signaling pathways, epigenetic modulation, immune system, lifestyle, JAK2V617F variant allele load, and exceptional germline alleles found in population-wide and hereditary cases are other possible factors involved in the development of JAK2V617F73-associated MPNs [ 71 , 72 ].…”

Section: Janus Kinase Gene ( Jak2 )mentioning

confidence: 99%

“…The latter is possibly related to individual characteristics (sex, associated inflammatory disease), and genetic abnormalities (driver genes, pathogenic genetic variants and other chromosomal aberrations) [ 71 ]. Different signaling pathways, epigenetic modulation, immune system, lifestyle, JAK2V617F variant allele load, and exceptional germline alleles found in population-wide and hereditary cases are other possible factors involved in the development of JAK2V617F73-associated MPNs [ 71 , 72 ]. The discovery of this genetic alteration has brought benefits for the therapy and diagnosis of MPNs; however, some questions remain unclear, such as the events that precede its acquisition, since it is not a germline genetic variant [ 29 ].…”

Section: Janus Kinase Gene ( Jak2 )mentioning

confidence: 99%

“…: NG_046969.1; HGNC ID: 6089) and Insulin like 4 ( INSL4 —RefSeq. : NC_000009.12; HGNC ID: 6087); the latter two are not expressed in the hematopoietic system [ 47 , 66 , 71 , 88 , 96 ] ( Figure 2 ).…”

Section: 46/1 Haplotypementioning

confidence: 99%

“… rs12686652 [ 89 ] Significantly associated with patients with PV in this case-control study, but no association with MPNs in the Japanese population. rs12335546 rs12343867 [ 71 , 89 , 90 , 99 , 100 , 101 , 102 ] Associated with positive JAK2V617F in the populations of Japan, China, and Taiwan, especially in individuals with PV; this is used as a haplotype marker. Association with splenomegaly has been reported and is in LD with other SNVs of haplotype 46/1.…”

Section: 46/1 Haplotypementioning

confidence: 99%

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The Contribution of JAK2 46/1 Haplotype in the Predisposition to Myeloproliferative Neoplasms

Paes

Silva

Tarragô

et al. 2022

IJMS

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Haplotype 46/1 (GGCC) consists of a set of genetic variations distributed along chromosome 9p.24.1, which extend from the Janus Kinase 2 gene to Insulin like 4. Marked by four jointly inherited variants (rs3780367, rs10974944, rs12343867, and rs1159782), this haplotype has a strong association with the development of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) because it precedes the acquisition of the JAK2V617F variant, a common genetic alteration in individuals with these hematological malignancies. It is also described as one of the factors that increases the risk of familial MPNs by more than five times, 46/1 is associated with events related to inflammatory dysregulation, splenomegaly, splanchnic vein thrombosis, Budd–Chiari syndrome, increases in RBC count, platelets, leukocytes, hematocrit, and hemoglobin, which are characteristic of MPNs, as well as other findings that are still being elucidated and which are of great interest for the etiopathological understanding of these hematological neoplasms. Considering these factors, the present review aims to describe the main findings and discussions involving the 46/1 haplotype, and highlights the molecular and immunological aspects and their relevance as a tool for clinical practice and investigation of familial cases.

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