The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features

Orazi, Attilio; Germing, Ulrich

doi:10.1038/leu.2008.119

Cited by 165 publications

(160 citation statements)

References 50 publications

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“…Unfortunately, detailed descriptions of BM findings are mostly lacking in these cases, and therefore, it can only be speculated that a considerable number of these occult MPN represent prodromal stages of the major MPN categories (PV, ET, initial-early stage PMF). Moreover, refractory anemia with ring sideroblasts (RARS-T) and thrombocytosis has to be considered, because of the problematic distinction between this overlap syndrome and MPN, particularly, when myelodysplastic features are not very conspicuous [42,43]. On the other hand, ring sideroblasts are not an uncommon finding in MPN and the recent demonstration of a relatively high frequency for JAK2V617F and MPL mutations [44][45][46][47][48][49][50][51][52][53] confirms previous clinicopathological studies about the heterogeneity of this disorder [54].…”

Section: Introductionsupporting

confidence: 61%

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: Introductionsupporting

confidence: 61%

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

Kvasnicka

Thiele

2009

American J Hematol

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“…32,33 CD34 ϩ cells from patients with RARS have a particular gene expression profile characterized by overexpression of mitochondria-related genes and, in particular, genes involved in heme synthesis (eg, ALAS2), 34 and reduced expression of ABCB7, a gene encoding a protein involved in the transport of iron/sulfur clusters from mitochondria to the cytoplasm. 35 RARS-T is a myeloid neoplasm with both myelodysplastic and myeloproliferative features at the molecular and clinical levels 23,36 that may develop from RARS through the acquisition of somatic mutations of JAK2, MPL, or other as-yet-unknown genes. 23 In this study, 79% of patients with RARS, 57.7% of those with RCMD-RS, and 66.7% of those with RARS-T carried somatic mutations of SF3B1 (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms

Malcovati

Papaemmanuil

Bowen

et al. 2011

Blood

457

350

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In a previous study, we identified somatic mutations of SF3B1, a gene encoding a core component of RNA splicing machinery, in patients with myelodysplastic syndrome (MDS). Here, we define the clinical significance of these mutations in MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). The coding exons of SF3B1 were screened using massively parallel pyrosequencing in patients with MDS, MDS/MPN, or acute myeloid leukemia (AML) evolving from MDS. Somatic mutations of SF3B1 were found in 150 of 533 (28.1%) patients with MDS, 16 of 83 (19.3%) with MDS/MPN, and 2 of 38 (5.3%) with AML. There was a significant association of SF3B1 mutations with the presence of ring sideroblasts (P < .001) and of mutant allele burden with their proportion (P = .002). The mutant gene had a positive predictive value for ring sideroblasts of 97.7% (95% confidence interval, 93.5%-99.5%). In multivariate analysis including established risk factors, SF3B1 mutations were found to be independently associated with better overall survival (hazard ratio = 0.15, P = .025) and lower risk of evolution into AML (hazard ratio = 0.33, P = .049). The close association between SF3B1 mutations and disease phenotype with ring sideroblasts across MDS and MDS/MPN is consistent with a causal relationship. Furthermore, SF3B1 mutations are independent predictors of favorable clinical outcome, and their incorporation into stratification systems might improve risk assessment in MDS.

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“…[3][4][5] Although more often a 'primary neoplasm', rare cases of secondary chronic myelomonocytic leukemia have been sporadically reported. In a recent study, 6 it was noted that a subset of patients with myelodysplastic syndrome developed monocytosis in the course of their disease.…”

mentioning

confidence: 99%

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

et al. 2013

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Primary myelofibrosis is a type of chronic myeloproliferative neoplasm characterized by progressive bone marrow failure with worsening cytopenia and in a subset of patients, progression to acute leukemia. Published data in patients with myelodysplastic syndromes have shown that the development of monocytosis in the course of myelodysplastic syndromes is associated with a poor prognosis. A similar occurrence has been only sporadically reported in patients with primary myelofibrosis. Over a period of four years we identified 10 out of 237 cases of primary myelofibrosis who developed persistent absolute monocytosis (41 Â 10 9 /l) during the course of disease (5 men and 5 women; median age/range: 68 years/52-82). Monocytosis developed at a median interval of 42 months from diagnosis (range: 1-180) and persisted for a median period of 23 months (range: 2-57). Five patients died after developing monocytosis (range: 20-188 months) and two experienced worsening disease and became transfusion dependent. Monocytosis was associated with increased white blood cells, decreased hemoglobin, decreased platelet count, and the presence of circulating blasts. In three cases, bone marrow biopsies after the onset of monocytosis showed marked myelomonocytic proliferation with morphological shifting from a typical primary myelofibrosis marrow appearance to aspects compatible with an overt 'secondary' chronic myelomonocytic leukemia. Before the development of monocytosis, 5 of 10 patients carried the JAK2V617F mutation; five patients showed karyotypic alterations. No change in JAK2 mutational status or cytogenetic evolution were associated with the development of monocytosis. Four of nine patients analyzed showed KRAS mutation in codon 12 or 13 with low allele burden. This is the first study correlating monocytosis developing in primary myelofibrosis patients with bone marrow morphology, laboratory data, molecular analysis and clinical follow-up. Development of monocytosis in patients with established primary myelofibrosis is associated with rapid disease progression and these patients should be considered as a high-risk group associated with short survival.

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The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features

Cited by 165 publications

References 50 publications

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

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