Molecular testing for <scp>JAK</scp>2, <scp>MPL</scp>, and <scp>CALR</scp> in myeloproliferative neoplasms

Xia, Daniel; Hasserjian, Robert P.

doi:10.1002/ajh.24578

Cited by 22 publications

(19 citation statements)

References 31 publications

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“…Mutations are now formally integrated into the WHO diagnostic criteria for PMF and other MPN . In this regard, a diagnosis of PV often requires demonstration of an associated JAK2 mutation and diagnosis of ET and PMF is strongly supported by the presence of JAK2 , CALR or MPL mutations; however, these mutations are not disease‐specific and their presence is not essential for an otherwise morphology‐based diagnosis . Genetic markers in PMF have also proven to be the primary determinants of survival and are now part of formal prognostic systems, such as MIPSS70+ version 2.0 and GIPSS; in this regard, ASXL1 and SRSF2 mutations and unfavorable karyotype have consistently been associated with inferior survival.…”

Section: Closing Commentsmentioning

confidence: 99%

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

2018

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Observation alone is advised for MIPSS70+ version 2.0 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic stem cell transplant is the preferred treatment of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. All other treatment approaches, including the use of JAK2 inhibitors, are mostly palliative and should not be used in the absence of clear treatment indications. Conventional treatment for anemia includes androgens, prednisone, thalidomide and danazol, for symptomatic splenomegaly hydroxyurea and ruxolitinib and for constitutional symptoms ruxolitinib. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for nonhepatosplenic EMH and extremity bone pain.

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Section: Closing Commentsmentioning

confidence: 99%

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

2018

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“…Besides JAK2V617F mutation, recent studies showed that somatic mutation at exon 9 of CALR accounts of 50~80% JAK2V617F-negative ET and MF patients. [5][6][7][8][9] It has diagnostic importance and also contributes to the clinical characteristics of ET patients; therefore, it is crucial to identify the mutations. [10][11][12][13][14][15] Although most of the mutations correspond to a 52 bp deletion (type 1) or a 5 bp insertion (type 2), there were more than 50 other mutations found.…”

Section: Methodsmentioning

confidence: 99%

Calreticulin mutation survey by high resolution melting method associated with unique presentations in essential thrombocythemic patients

Liu

Lee

Yeh

et al. 2020

Mediterr J Hematol Infect Dis

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Somatic mutations of exon 9 of calreticulin gene (CALR) were diagnosis and prognosis importance found in patients with JAK2V617F-negative essential thrombocythemia (ET). We survey CALR and JAK2 mutations in our ET patients and study the relationship between mutations and clinical presentations. A total of 60 ET patients were enrolled in the study, and CALR mutations were studied by high resolution melting (HRM) methods and sequencing in JAK2V617F-negative group retrospectively. Clinical manifestations were reviewed retrospectively from chart records. Twenty-one CALR mutations showed eight types of specific melting curves detected by the HRM method and sequencing validation among 26 JAK2 V617F-negative patients. Compared with JAK2 mutations, patients with CALR mutations were younger and had a higher platelet count, lower white cell counts, and lower hemoglobin levels significantly (p<0.05). From our study, HRM methods revealed unique curve types in screening for CALR mutations screening even for complicated mutations. The mutations can be identification rapidly, and cost-effectively by HRM method than other tools. The clinical presentations of CALR mutations from JAK2 mutations showed significant differences and should be checked in ET patients.

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“…[11][12][13][14] Standard procedures were followed for driver mutation screening. 15 April 2018 and data collected via medical records or in certain cases, by directly contacting patients or their physicians. Risk-stratification was performed using the three-tiered prognostic model international prognostic score for ET (IPSET).…”

Section: Methodsmentioning

confidence: 99%

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

et al. 2018

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First‐line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second‐line drugs of choice include pegylated interferon‐α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928‐1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis‐free (MFFS) and thrombosis‐free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1‐1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7‐6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.

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Molecular testing for JAK2, MPL, and CALR in myeloproliferative neoplasms

Cited by 22 publications

References 31 publications

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

Calreticulin mutation survey by high resolution melting method associated with unique presentations in essential thrombocythemic patients

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

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