Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Bernard, Elsa; Tuechler, Heinz; Greenberg, Peter L.; Hasserjian, Robert P.; Ossa, Juan Arango; Nannya, Yasuhito; Devlin, Sean M.; Creignou, Maria; Pinel, Philippe; Monnier, Lily; Gundem, Gunes; Medina-Martínez, Juan S.; Domenico, Dylan; Jädersten, Martin; Germing, Ulrich; Sanz, Guillermo; Loosdrecht, Arjan A. van de; Kosmider, Olivier; Follo, Matilde Y.; Thol, Felicitas; Zamora, Lurdes; Pinheiro, Ronald Feitosa; Pellagatti, Andrea; Elias, Harold; Haase, Detlef; Ganster, Christina; Adès, Lionel; Tobiasson, Magnus; Palomo, Laura; Porta, Matteo Giovanni Della; Takaori‐Kondo, Akifumi; Ishikawa, Takayuki; Chiba, Shigeru; Kasahara, Senji; Miyazaki, Yasushi; Viale, Agnès; Huberman, Kety; Fenaux, Pierre; Beličková, Monika; Savona, Michael R.; Klimek, Virginia M.; Santos, Fabio P S; Boultwood, Jacqueline; Kotsianidis, Ιoannis; Santini, Valeria; Solé, Françesc; Platzbecker, Uwe; Heuser, Michael; Valent, Peter; Ohyashiki, Kazuma; Finelli, Carlo; Voso, Maria Teresa; Shih, Lee‐Yung; Fontenay, Michaëla; Jansen, Joop H.; Cervera, José; Gattermann, Norbert; Ebert, Benjamin L.; Bejar, Rafael; Malcovati, Luca; Cazzola, Mario; Ogawa, Seishi; Hellström‐Lindberg, Eva; Papaemmanuil, Elli

doi:10.1056/evidoa2200008

Cited by 396 publications

(410 citation statements)

References 25 publications

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“…Conversion of all these elements into a numerical score generates five risk categories for MDS progression (IPSS-R)(Very Low, Low, Intermediate, High, Very High) [ 29 ]. A new Molecular International Prognosis Scoring System (M-IPSS) prognostic score was presented to the American Society of Hematology in 2021, integrating the mutational status of 38 gene loci that would allow for better risk discrimination as well as the reclassification of more than half of MDS patients into six risk strata (Very Low, Low, Moderate Low, Moderate High, High, Very High) [ 30 ]. The mutational status of UBA1 is not taken into account in the diagnosis and prognosis of MDS, related maybe to the recent description of this new syndrome.…”

Section: Vexas and Myelodysplastic Syndromementioning

confidence: 99%

VEXAS Syndrome: A Novelty in MDS Landscape

Templé

Kosmider

2022

Diagnostics

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Fever, inflammation and vacuoles in hematopoietic cells represent the main features associated with VEXAS syndrome, a new prototype of autoinflammatory disorders genetically characterized by somatic mutation of the UBA1 gene which encodes the enzyme1-activating enzyme (E1) required for ubiquitin signaling. Described very recently, patients with VEXAS syndrome present a systemic autoinflammatory syndrome associated with hematological impairments, especially cytopenias whose pathophysiology is mainly non-elucidated. Initially diagnosed in elderly male patients, VEXAS syndrome was frequently associated with a diagnosis of myelodysplastic syndromes (MDS) leading the medical community to first consider VEXAS syndrome as a new subtype of MDS. However, since the first description of VEXAS patients in 2021, it appears from the multitude of case reports that MDS associated with VEXAS are different from the classically described MDS.

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Section: Vexas and Myelodysplastic Syndromementioning

confidence: 99%

VEXAS Syndrome: A Novelty in MDS Landscape

Templé

Kosmider

2022

Diagnostics

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“…Myelodysplastic syndromes (MDS) are hematopoietic stem cell neoplasms characterized by the presence of cytopenia and dysplasia [ 28 ]. In the vast majority of MDS patients, the clonal nature of the disease can be demonstrated by chromosomal analysis and molecular genetics that identify somatic genetic alterations in >90% of patients [ 30 , 31 ]. Thus, the differential diagnosis between CCUS and MDS primarily relies on the presence or absence of dysplasia in bone marrow morphology ( Table 2 ).…”

Section: Chip and Hematologic Neoplasmsmentioning

confidence: 99%

Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential in Hematology and Cardiovascular Disease

Hoermann

2022

Diagnostics

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Liquid profiling uses circulating tumor DNA (ctDNA) for minimal invasive tumor mutational profiling from peripheral blood. The presence of somatic mutations in peripheral blood cells without further evidence of a hematologic neoplasm defines clonal hematopoiesis of indeterminate potential (CHIP). CHIP-mutations can be found in the cell-free DNA (cfDNA) of plasma, are a potential cause of false positive results in liquid profiling, and thus limit its usage in screening settings. Various strategies are in place to mitigate the effect of CHIP on the performance of ctDNA assays, but the detection of CHIP also represents a clinically significant incidental finding. The sequelae of CHIP comprise the risk of progression to a hematologic neoplasm including therapy-related myeloid neoplasms. While the hematological risk increases with the co-occurrence of unexplained blood count abnormalities, a number of non-hematologic diseases have independently been associated with CHIP. In particular, CHIP represents a major risk factor for cardiovascular disease such as atherosclerosis or heart failure. The management of CHIP requires an interdisciplinary setting and represents a new topic in the field of cardio-oncology. In the future, the information on CHIP may be taken into account for personalized therapy of cancer patients.

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“…In MDS, contrary to U2AF1 mutations, U2FA2 mutations are rare and recurrent events in myeloid pathologies, with a frequency of 1% or less [ 125 ]. They have a prognostic value [ 7 , 126 ], as they are associated with high-risk MDS and AML [ 127 ].…”

Section: Other Mutated Splicing Genes With a Prognostic Value: ...mentioning

confidence: 99%

“…Taken alone, each gene can play its own distinct role in the molecular pathogenesis of MDS and triggers its own specific landscape of splicing alterations. Most of these genes are included in the recently proposed molecular IPSS-M [ 126 ]. Scientific literature accumulates on that subject but more research needs to be done (review in [ 135 ]).…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Cytogenetic and Genetic Abnormalities with Diagnostic Value in Myelodysplastic Syndromes (MDS): Focus on the Pre-Messenger RNA Splicing Process

et al. 2022

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Myelodysplastic syndromes (MDS) are considered to be diseases associated with splicing defects. A large number of genes involved in the pre-messenger RNA splicing process are mutated in MDS. Deletion of 5q and 7q are of diagnostic value, and those chromosome regions bear the numbers of splicing genes potentially deleted in del(5q) and del(7q)/-7 MDS. In this review, we present the splicing genes already known or suspected to be implicated in MDS pathogenesis. First, we focus on the splicing genes located on chromosome 5 (HNRNPA0, RBM27, RBM22, SLU7, DDX41), chromosome 7 (LUC7L2), and on the SF3B1 gene since both chromosome aberrations and the SF3B1 mutation are the only genetic abnormalities in splicing genes with clear diagnostic values. Then, we present and discuss other splicing genes that are showing a prognostic interest (SRSF2, U2AF1, ZRSR2, U2AF2, and PRPF8). Finally, we discuss the haploinsufficiency of splicing genes, especially from chromosomes 5 and 7, the important amplifier process of splicing defects, and the cumulative and synergistic effect of splicing genes defects in the MDS pathogenesis. At the time, when many authors suggest including the sequencing of some splicing genes to improve the diagnosis and the prognosis of MDS, a better understanding of these cooperative defects is needed.

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Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Cited by 396 publications

References 25 publications

VEXAS Syndrome: A Novelty in MDS Landscape

VEXAS Syndrome: A Novelty in MDS Landscape

Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential in Hematology and Cardiovascular Disease

Cytogenetic and Genetic Abnormalities with Diagnostic Value in Myelodysplastic Syndromes (MDS): Focus on the Pre-Messenger RNA Splicing Process

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