JAK2V617F allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis

Hussein, Kais; Theophile, Katharina; Neuhoff, Nils von; Buhr, T.; Schlué, Jérôme; Büsche, Guntram; Kreipe, Hans

doi:10.1016/j.exphem.2009.07.005

Cited by 72 publications

(66 citation statements)

References 40 publications

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“…Therefore, this marker is only useful in discriminating MPN from reactive thrombocytosis [1,3]. On the other hand, it has to be emphasized that significant differences in the JAK2V617F allele burden were described between ET and early PMF [75]. As an independent marker, this feature validates very nicely corresponding BM findings, and thus, supports our concept of differentiating so-called ET [92][93][94][95].…”

Section: Essential Thrombocythemiasupporting

confidence: 73%

“…In this context, the question arises how many of the JAK2V617F-positive patients with splanchnic vein thrombosis, Budd Chiari syndrome or cerebral thrombosis may actually present early stage or smouldering PV according to their BM morphology, especially when associated with Epo levels below the normal range [34][35][36][37][38][39]41]. Moreover, it was found that increase in JAK2V617F allele burden during follow-up indicates overt PV transformation in cases which initially mimicked ET and presented without significant erythrocytosis [75,76].…”

Section: Polycythemia Veramentioning

confidence: 99%

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Prodromal myeloproliferative neoplasms: The 2008 WHO classification

Kvasnicka

Thiele

2009

American J Hematol

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The concept of prodromal chronic myeloproliferative neoplasms has been endorsed by the WHO classification implicating a stepwise evolution of disease. Histology of the bone marrow (BM) and borderline to mildly expressed clinical features play a pivotal role for diagnosing prefibrotic-early primary myelofibrosis. By lowering the platelet count for essential thrombocythemia and regarding BM morphology, early manifestations are tackled. Pre-polycythemic stages of polycythemia vera with a low hemoglobin level at onset are diagnosed by positive JAK2V617F mutation status, a low erythropoietin value, and characteristic BM features. The revised WHO classification incorporates hematological, morphological, and moleculargenetic parameters to generate a consensus-based working diagnosis. Am. J. Hematol. 85:62-69, 2010. V

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Section: Essential Thrombocythemiasupporting

confidence: 73%

Section: Polycythemia Veramentioning

confidence: 99%

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

Kvasnicka

Thiele

2009

American J Hematol

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“…In a study involving 230 patients with early/prefibrotic PMF and 90 ET subjects, diagnosed based on histology, Hussein et al 47 observed comparable frequencies of JAK2V617F mutation (47 of 90 were mutated in ET (52%) versus 55% in early/prefibrotic PMF (52 of 95)); 50 similar data were reported by the large IWG-MRT study on 891 ET (61% were JAK2 mutated) and 180 early/prefibrotic PMF patients (58%). 23 Hussein et al 47 also reported that the V617F allelic burden was lower in ET (median 24%, range 5-40%) than in early/ prefibrotic PMF (38%, range, 7-92%). 54 Although statistically significant, this observation has modest clinical relevance due to the very close median levels and the large overlapping of the two patient populations.…”

Section: Molecular-genetic Findingssupporting

confidence: 65%

Problems and pitfalls regarding WHO-defined diagnosis of early/prefibrotic primary myelofibrosis versus essential thrombocythemia

et al. 2013

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Reproducibility and clinical usefulness of the WHO classification of chronic myeloproliferative neoplasm (MPN) persist to be a controversial issue. Major arguments are focused on the critical impact of histopathology, particularly concerning the distinction between essential thrombocythemia (ET) versus early/prefibrotic primary myelofibrosis (PMF). Regarding bone marrow morphology, WHO guidelines strictly require the recognition of characteristic histological patterns based on standardized features and a consensus of clinical and molecular-genetic data. Molecular-genetic findings as JAK2V617F, may aid to exclude reactive thrombocytosis, although in ET and PMF only 50-60% of the cases show these aberrations. Considerable doubts over the existence of early/prefibrotic PMF have been expressed with the consequence to include this entity in the ET category. On the other hand, it has to be argued that some of the critical studies failed to adhere very strictly to the WHO guidelines. Contrasting this situation, recently published retrospective and prospective clinico-pathological studies featuring the WHO criteria provided an important information on disease outcomes supporting the existence of early/prefibrotic PMF as a distinct clinico-pathologic entity in patients presenting clinically with ET. Therefore, this controversy suggests a scientific project, including the community of pathologists and hematologists, for providing sound, objective and reproducible criteria for diagnosing early/prefibrotic PMF.

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“…In addition, our cohort of patients with WHO-ET was characterized by a low JAK2-V617F allele burden, which confirms the results of a significantly lower JAK2-V617F allele burden in WHO-ET vs early-prefibrotic PMF reported in a cohort of patients primarily defined by bone marrow morphologic features. 44 Controversy persists concerning whether the histologic bone marrow criteria proposed by the WHO for the classification of ET, particularly the discrimination between WHO-ET vs early-prefibrotic PMF, is reproducible. 18 Contrasting 1 group, 45 other investigators confirmed their ability to discriminate between WHO-ET and the thrombocythemic manifestations of early-prefibrotic PMF.…”

Section: Discussionmentioning

confidence: 99%