Molecular characterisation of triple negative essential thrombocythaemia patients by platelet analysis and targeted sequencing

Angona, Anna; Fernández-Rodríguez, Concepción; Alvarez‐Larrán, A.; Camacho, Laura; Longarón, Raquel; Torres, Eduardo Mateos; Pairet, Silvia; Besses, Carlos; Bellosillo, Beatríz

doi:10.1038/bcj.2016.75

Cited by 24 publications

(26 citation statements)

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“…Contrary to TN primary MF patients [14], it has been reported that TN ET patients have a relatively good prognosis, with 80% overall survival at 5-year follow-up [7], and with no transformation to acute leukaemia or secondary MF [15]. BM biopsies of TN ET in our series showed a high cellularity, the lowest number of cloudy megakaryocytes, and a low number of dysmorphic megakaryocytes, all histological features suggesting a favourable evolution.…”

Section: Discussioncontrasting

confidence: 43%

JAK2V617F, CALR, and MPL Mutations and Bone Marrow Histology in Patients with Essential Thrombocythaemia

et al. 2018

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Introduction: Mutations in the JAK2, CALR, and MPL genes have been shown to have prognostic value in essential thrombocythaemia (ET), but no clear association with morphological changes has been reported so far. We investigated the possible correlation between gene mutations and histopathological features in bone marrow (BM) biopsies of patients with ET. Methods: Marrow cellularity, fibrosis, and the number of total and dysmorphic megakaryocytes and clusters of megakaryocytes were compared to gene mutations in 90 cases of ET at diagnosis. Results: The JAK2^V617F mutation was found in 58.9%, CALR in 28.9%, and MPL in 4.4% of the cases, and 7.8% were triple-negative. JAK2^V617F-mutated ET showed a high BM cellularity, the lowest number of clusters of megakaryocytes and the highest number of dysmorphic megakaryocytes; CALR-mutated ET showed a reduced BM cellularity, many clusters of large megakaryocytes, and very few dysmorphic megakaryocytes; MPL-mutated ET showed the lowest BM cellularity, the highest number of clustered and large megakaryocytes, and the lowest number of dysmorphic megakaryocytes. Triple-negative ET cases had the highest BM cellularity. Conclusions: Distinct morphological patterns were associated with gene mutations in ET, supporting the classification of ET into different subtypes.

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Section: Discussioncontrasting

confidence: 43%

JAK2V617F, CALR, and MPL Mutations and Bone Marrow Histology in Patients with Essential Thrombocythaemia

et al. 2018

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“…[5][6][7][8][9] In order to address this issue, several groups have recently applied either whole exome sequencing and/or targeted exon sequencing to triple negative MPN, particularly ET cases, and which have informed further understanding of the molecular pathogenesis of this group of patients. [10][11][12] In addition to sporadic mutations in epigenetic modifying (ASXL1, TET2), spliceosome (SF3B1, SRSF2), and regulators of cytokine signaling (CBL, SH2B3) genes, a significant number of mutations were detected in both the JAK2 and MPL genes, strikingly in exons not normally mutated in MPN (Fig. 2).…”

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confidence: 99%

“…2). [10][11][12] All novel MPL mutations and 2 novel JAK2 mutations detected by one group resulted in a gain of function by inducing ligand-independent JAK2-STAT5 signaling when analyzed in functional assays. 10 These findings were confirmed by demonstration of thrombopoietin hypersensitivity and independence of 2 such novel MPL mutations in a further study.…”

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confidence: 99%

“…11 The diversity of MPL mutations occurring in the extracellular domain-encoding exons of triple negative MPN has been further expanded. 12 Clearly these findings have important implications for molecular diagnostics which aims to distinguish true MPN from reactive causes. Those diagnostic approaches that target specific mutations such as allele-specific PCR will not identify these, admittedly rare, variants.…”

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confidence: 99%

“…[16][17] It must be noted that a significant number of MPN patients classified as triple negative have no detectable alternative JAK2 or MPL mutations, nor any evidence of clonal hematopoiesis by X chromosome inactivation patterns. [10][11][12] Whether these cases, analogous to a larger proportion of pediatric patients classified as MPN, truly have a clonal malignancy is questionable. 18 Re-consideration of the role of haematopoietic clonality assessment by X-chromosome inactivation patterns in triplenegative MPN may be necessary, however these approaches apply only to female patients, require considerable interpretation, and have been further confounded by the recent description of polyclonal hematopoiesis in some female MPN patients.…”

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confidence: 99%

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Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics

Langabeer

2016

JAK-STAT

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ABSTRACT. The majority of patients with classical myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia, and primary myelofibrosis harbor distinct diseasedriving mutations within the JAK2, CALR, or MPL genes. The term triple-negative has been recently applied to those MPN without evidence of these consistent mutations, prompting whole or targeted exome sequencing approaches to determine the driver mutational status of this subgroup. These strategies have identified numerous novel mutations that occur in alternative exons of both JAK2 and MPL, the majority of which result in functional activation. Current molecular diagnostic approaches may possess insufficient coverage to detect these alternative mutations, prompting further consideration of targeted exon sequencing into routine diagnostic practice. How to incorporate these illuminating findings into the expanding molecular diagnostic algorithm for MPN requires continual attention.

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Essential thrombocythaemia

Ravi¹,

Kundaje²,

Shenoy³

2021

Haematology

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Molecular characterisation of triple negative essential thrombocythaemia patients by platelet analysis and targeted sequencing

Cited by 24 publications

References 13 publications

<b><i>JAK2</i></b><sup>V617F</sup>, <b><i>CALR</i></b>, and <b><i>MPL</i></b> Mutations and Bone Marrow Histology in Patients with Essential Thrombocythaemia

<b><i>JAK2</i></b><sup>V617F</sup>, <b><i>CALR</i></b>, and <b><i>MPL</i></b> Mutations and Bone Marrow Histology in Patients with Essential Thrombocythaemia

Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics

Essential thrombocythaemia

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