Clinical and biological characterization of patients with low (0.1-2%) JAK2V617F allele burden at diagnosis

Lippert, Éric; Mansier, Olivier; Migeon, Marina; Denys, Barbara; Nilsson, Asa; Rosmond, Carolina; Lodé, Laurence; Ugo, Valérie; Lascaux, Axelle; Bellosillo, Beatríz; Martínez‐López, Joaquín; Naguib, Dina; Gachard, Nathalie; Maroc, N; Hermouet, Sylvie

doi:10.3324/haematol.2014.107656

Cited by 25 publications

(17 citation statements)

References 12 publications

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“…It should be mentioned that in our cohort of the MPN patients, the molecular evaluation was carried out with the help of RT‐PCR in case of the BCR‐ABL1 fusion gene (the sensitivity of approximately 10 −5 ) and melting curve‐based LightCycler assay in terms of the JAK2 gene assessment (the sensitivity of the method depends on the mutation sequence and reaches 1% of the allelic burden) and may miss patients with low (0.1%‐1%) JAK2 V617F and MPL allele burden. It should be kept in mind, however, that according to the recent data, the finding of low allele burden of JAK2 V617F is not to be considered a sufficient evidence to diagnose MPN and should prompt the search for additional mutations in the JAK2 gene in case of erythrocytosis and in the CALR and MPL genes in other cases …”

Section: Discussionmentioning

confidence: 99%

Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Lewandowski

Gniot

Wojtaszewska

et al. 2018

Int J Lab Hematology

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Section: Discussionmentioning

confidence: 99%

Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Lewandowski

Gniot

Wojtaszewska

et al. 2018

Int J Lab Hematology

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“…One such assay using a specific reverse primer had an excellent detection level and specificity and is recommended by the European LeukemiaNet . Selection of a PCR primer that anneals 5′ of the mutation may be beneficial to avoid false negatives caused by the rare, alternative JAK2 exon 14 mutations .…”

Section: Jak2 V617f Quantitationmentioning

confidence: 99%

Molecular diagnostics of myeloproliferative neoplasms

Langabeer

Andrikovics

Asp

et al. 2015

European J of Haematology

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Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN.

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“…<1% of mutation loads) [5, 26, 32]. Additionally, many recent studies have shown that a small clonal hematopoiesis may be present also in otherwise healthy subjects at low level (0.03–1%) [27, 32–38]. In the context of highly sensitive allele-specific assays and low mutant AB in the peripheral blood, the possibility of both false-positive and false-negative test results is not negligible [5, 32].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the interlaboratory variability and robustness of JAK2V617F mutation assays: A study involving a consortium of 19 Italian laboratories

et al. 2017

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To date, a plenty of techniques for the detection of JAK2V617F is used over different laboratories, with substantial differences in specificity and sensitivity. Therefore, to provide reliable and comparable results, the standardization of molecular techniques is mandatory.A network of 19 centers was established to 1) evaluate the inter- and intra-laboratory variability in JAK2V617F quantification, 2) identify the most robust assay for the standardization of the molecular test and 3) allow consistent interpretation of individual patient analysis results. The study was conceived in 3 different rounds, in which all centers had to blindly test DNA samples with different JAK2V617F allele burden (AB) using both quantitative and qualitative assays.The positivity of samples with an AB < 1% was not detected by qualitative assays. Conversely, laboratories performing the quantitative approach were able to determine the expected JAK2V617F AB. Quantitative results were reliable across all mutation loads with moderate variability at low AB (0.1 and 1%; CV = 0.46 and 0.77, respectively). Remarkably, all laboratories clearly distinguished between the 0.1 and 1% mutated samples.In conclusion, a qualitative approach is not sensitive enough to detect the JAK2V617F mutation, especially at low AB. On the contrary, the ipsogen JAK2 MutaQuant CE-IVD kit resulted in a high, efficient and sensitive quantification detection of all mutation loads. This study sets the basis for the standardization of molecular techniques for JAK2V617F determination, which will require the employment of approved operating procedures and the use of certificated standards, such as the recent WHO 1st International Reference Panel for Genomic JAK2V617F.

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Clinical and biological characterization of patients with low (0.1-2%) JAK2V617F allele burden at diagnosis

Cited by 25 publications

References 12 publications

Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Molecular diagnostics of myeloproliferative neoplasms

Assessment of the interlaboratory variability and robustness of JAK2V617F mutation assays: A study involving a consortium of 19 Italian laboratories

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