BCR::ABL1-negative myeloproliferative neoplasms in the era of next-generation sequencing

Mroczkowska-Bękarciak, Aleksandra; Wróbel, Tomasz

doi:10.3389/fgene.2023.1241912

Cited by 4 publications

(4 citation statements)

References 94 publications

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“…A query of the American Association for Cancer Research (AACR) Project GENIE public database in cBioportal [32] found 299 samples from 202 cases documented as PMF (https://genie.cbioportal.org/study?id=6562046bb01fff74fbb6c576 (accessed on 25 November 2023)). In these 299 samples, in addition to JAK2 (44.8%), CALR (14.7%), and MPL (9.4%) mutations, the prevalence of other mutations is similar to those reported by other studies [29,31,33,34]. Table 1 lists the prevalence of relatively frequent non-driver mutations and the most common mutations or mutation types cataloged in the GENIE database.…”

Section: Additional Mutationssupporting

confidence: 77%

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Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements

Verma,

Papadantonakis,

Peker Barclift

et al. 2024

Cancers

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Myelofibrosis (MF) is an essential element of primary myelofibrosis, whereas secondary MF may develop in the advanced stages of other myeloid neoplasms, especially polycythemia vera and essential thrombocythemia. Over the last two decades, advances in molecular diagnostic techniques, particularly the integration of next-generation sequencing in clinical laboratories, have revolutionized the diagnosis, classification, and clinical decision making of myelofibrosis. Driver mutations involving JAK2, CALR, and MPL induce hyperactivity in the JAK-STAT signaling pathway, which plays a central role in cell survival and proliferation. Approximately 80% of myelofibrosis cases harbor additional mutations, frequently in the genes responsible for epigenetic regulation and RNA splicing. Detecting these mutations is crucial for diagnosing myeloproliferative neoplasms (MPNs), especially in cases where no mutations are present in the three driver genes (triple-negative MPNs). While fibrosis in the bone marrow results from the disturbance of inflammatory cytokines, it is fundamentally associated with mutation-driven hematopoiesis. The mutation profile and order of acquiring diverse mutations influence the MPN phenotype. Mutation profiling reveals clonal diversity in MF, offering insights into the clonal evolution of neoplastic progression. Prognostic prediction plays a pivotal role in guiding the treatment of myelofibrosis. Mutation profiles and cytogenetic abnormalities have been integrated into advanced prognostic scoring systems and personalized risk stratification for MF. Presently, JAK inhibitors are part of the standard of care for MF, with newer generations developed for enhanced efficacy and reduced adverse effects. However, only a minority of patients have achieved a significant molecular-level response. Clinical trials exploring innovative approaches, such as combining hypomethylation agents that target epigenetic regulators, drugs proven effective in myelodysplastic syndrome, or immune and inflammatory modulators with JAK inhibitors, have demonstrated promising results. These combinations may be more effective in patients with high-risk mutations and complex mutation profiles. Expanding mutation profiling studies with more sensitive and specific molecular methods, as well as sequencing a broader spectrum of genes in clinical patients, may reveal molecular mechanisms in cases currently lacking detectable driver mutations, provide a better understanding of the association between genetic alterations and clinical phenotypes, and offer valuable information to advance personalized treatment protocols to improve long-term survival and eradicate mutant clones with the hope of curing MF.

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Section: Additional Mutationssupporting

confidence: 77%

“…other studies [29,31,33,34]. Table 1 lists the prevalence of relatively frequent non-driver mutations and the most common mutations or mutation types cataloged in the GENIE database.…”

Section: Additional Mutationsmentioning

confidence: 99%

Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements

Verma,

Papadantonakis,

Peker Barclift

et al. 2024

Cancers

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“…Figure 2 provides a comprehensive view of the gene mutation landscapes within each patient with MN, considering the WHO-HAEM5 reclassified disease categories. [ 4 , 12 ] Genes were further organized into distinct functional groups, adapted from the relevant literature. [ 13 ] When interpreting gene mutation status, it is worth noting that in addition to pathogenic mutations, some mutations of uncertain significance, often with multiple coexisting mutations, are often found in MPN (Table 3 , Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

NGS panel enhance precise diagnosis of myeloid neoplasms under WHO-HAEM5 and International Consensus Classification: An observational study

Ye,

Zheng,

et al. 2024

Medicine

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This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) and the International Consensus Classification (ICC) of Myeloid Tumors. A cohort of 112 patients diagnosed with MN according to the revised fourth edition of the WHO classification (WHO-HAEM4R) underwent testing with a 141-gene NGS panel for hematological diseases. Ancillary studies were also conducted, including bone marrow cytomorphology and routine cytogenetics. The cases were then reclassified according to WHO-HAEM5 and ICC to assess the practical impact of these 2 classifications. The mutation detection rates were 93% for acute myeloid leukemia (AML), 89% for myelodysplastic syndrome (MDS), 94% for myeloproliferative neoplasm (MPN), and 100% for myelodysplasia/myeloproliferative neoplasm (MDS/MPN) (WHO-HAEM4R). NGS provided subclassified information for 26 and 29 patients with WHO-HAEM5 and ICC, respectively. In MPN, NGS confirmed diagnoses in 16 cases by detecting JAK2, MPL, or CALR mutations, whereas 13 “triple-negative” MPN cases revealed at least 1 mutation. NGS panel testing for hematological diseases improves the diagnosis and classification of MN. When diagnosed with ICC, NGS produces more classification subtype information than WHO-HAEM5.

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“…Philadelphia-negative (Ph−) chronic myeloproliferative neoplasms are clonal diseases that arise from a pluripotent hematopoietic stem cell. They include, among others, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) [1].…”

Section: Introductionmentioning

confidence: 99%

Retinal Vessel Analysis and Microvascular Abnormalities in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms

Roszkowska,

Leanza,

Aragona

et al. 2024

JCM

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Background: Philadelphia-negative chronic myeloproliferative neoplasms are a group of clonal hematopoietic disorders including polycythemia vera, essential thrombocythemia, and primary myelofi-brosis. These neoplasms are characterized by an increased risk of thrombotic complications. Several studies have highlighted that the study of vessels of the retina offers the opportunity to visualize, in vivo, the damage to microcirculation that is common in various systemic pathologies. Methods: in our study, forty patients underwent an ophthalmological examination, using non-invasive imaging tech-niques, for analyses of their retinal vascularization. The objective was to correlate the findings ob-tained from this study of the retina with different markers of thrombotic risk, to demonstrate the usefulness of studying retinal vessels as a possible new prognostic biomarker of thrombotic risk in patients affected by Philadelphia-negative chronic myeloproliferative neoplasms. Results: retinal imaging demonstrated changes in the microcirculation, with a reduced vascular density of the deep and superficial capillary plexuses with respect to a normal group, and a correlation between retinal changes and blood parameters. Conclusions: additional research will allow us to determine whether retinal changes in individuals with chronic myeloproliferative neoplasms could be predictive of the development of thrombotic events in these subjects.

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BCR::ABL1-negative myeloproliferative neoplasms in the era of next-generation sequencing

Cited by 4 publications

References 94 publications

Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements

Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements

NGS panel enhance precise diagnosis of myeloid neoplasms under WHO-HAEM5 and International Consensus Classification: An observational study

Retinal Vessel Analysis and Microvascular Abnormalities in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms

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