The mutational landscape of 18 investigated genes clearly separates four subtypes of myelodysplastic/myeloproliferative neoplasms

Meggendorfer, Manja; Jeromin, Sabine; Haferlach, Claudia; Kern, Wolfgang; Haferlach, Torsten

doi:10.3324/haematol.2017.183160

Cited by 41 publications

(42 citation statements)

References 15 publications

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“…5 Meggendorfer M demonstrated that MDS/MPN-U tended to be associated with mutations in epigenetic regulation, the JAK-STAT pathway and splicing but marginally carried RAS pathway-associated mutations. 6 In addition, RAS pathway mutations often coexist with RUNX1, GATA2 , and STAG2 mutations. 7 The patient harboured KRAS, EZH2, RUNX1, STAG2, PLCG1 and CREBBP mutations that were combined epigenetic regulator, transcription factor, and growth factor signalling pathway-associated mutations.…”

Section: Discussionmentioning

confidence: 99%

Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of KRAS

Luo

et al. 2020

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Myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/ MPN-U) is a subtype of MDS/MPN that exhibits a combination of the features of both MDS and MPN. To date, no curative treatment is available for MDS/MPN-U; however, previous studies have suggested a potential survival advantage for ruxolitinib and hypomethylating agents. We reported a case of a JAK2-negative but KRAS-positive MDS/MPN-U patient treated with ruxolitinib plus decitabine. After treatment, the patient's clinical symptoms were moderated, and the size of the spleen and the peripheral blood cell counts were reduced. These effects might be due to the regimen's ability to reduce STAT5 activation and upregulate microRNA-181c to downregulate the variant allele frequency (VAF) of KRAS.

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Section: Discussionmentioning

confidence: 99%

Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of KRAS

Luo

et al. 2020

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“…Atypical CML (aCML) is a rare entity among MDS/MPN overlap syndromes characterized by the absence of the BCR-ABL1 fusion gene as well as rearrangements of the PDGFRA, PDGFRB or FGFR1 genes [ 24 ]. ASXL1 (20–70%), SETBP1 (25–30%) and TET2 (43%) mutations are the most common mutations detected in aCML [ 66 , 67 ]. SETBP1 mutations correlate with worse survival outcomes [ 68 ].…”

Section: Srsf2 In Mds/mpn Overlap Syndromesmentioning

confidence: 99%

“…SETBP1 mutations correlate with worse survival outcomes [ 68 ]. A high frequency of SRSF2 mutations (40%) was reported among a cohort of 60 aCML [ 54 ] while its frequency has been reported variably in other studies [ 67 , 69 , 70 ]. SRSF2 mutation appears more frequently with ASXL1-mut ( p = 0.01) and SETBP1-mut ( p = 0.004) compared to WT.…”

Section: Srsf2 In Mds/mpn Overlap Syndromesmentioning

confidence: 99%

“…This disease has now been accepted as a separate entity in 2016 revision of WHO classification [ 2 ]. Splicing factor mutations are common in this group, with SF3B1 being the most frequently occurring mutation (85–91%) [ 67 , 71 , 72 ]. SF3B1 mutation status is strongly associated with increased number of ringed sideroblasts ( p = 0.006).…”

Section: Srsf2 In Mds/mpn Overlap Syndromesmentioning

confidence: 99%

“…MDS/MPN-U is another rare entity with heterogenous dysplastic and proliferative features except some distinct associations such as isolated trisomy 8 seen in about 15% of cases compared to MDS (5%) and MPN (4%) [ 73 ]. JAK2 mutation is one of the most common (23–66%) mutations reported in this group [ 67 ] but has not been reported to have prognostic importance. Other mutations occur in comparable frequencies, ASXL1 and TET2 (36%), U2AF1 (18%), SRSF2 (15%) and SF3B1 (13%).…”

Section: Srsf2 In Mds/mpn Overlap Syndromesmentioning

confidence: 99%

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SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms

et al. 2018

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Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach. E7107, a spliceosome inhibitor, has been shown to differentially inhibit splicing more in SRSF2-mutant cells leading to decreased leukemia burden in mice. H3B-8800 is a small molecule modulator of spliceosome complex and has been shown to lower leukemia burden in SRSF2-P95H mutant mice. This review focuses on the incidence of mutant SRSF2 across various MMOS as well as recent clinical development of spliceosome inhibitors.

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2021

Haematology

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Anaplasticlargecelllymphomawith haemophagocyticsyndrome ALK-negativeanaplasticlargecelllymphoma: 1) GenerallyoccursatanolderagethanALK-positivecases 2) HasabetterprognosisthanALK-positiveanaplasticlargecelllymphoma 3) Hassimilarhistologicalandimmunophenotypicfeaturestobreastimplant-associatedanaplasticlargecelllymphoma 4) Isusuallyassociatedwitht(2;5)(p23.2-23.1;q35.1) 5) Usuallypresentswithlocaliseddisease Correct answers 1, 3ALK-negativeanaplasticlargecelllymphomatypicallyoccursatanolderagethanALK-positive casesandhasaworseprognosis.PresentationisusuallywithstageIIIorIVdisease.Althoughthey arehistologicallyindistinguishable,thesearequitedifferentconditions.ItisALK-positivecases thatareassociatedwitht(2;5),leadingtoformationofanNPM1-ALKfusiongene.Breastimplantassociatedcasesarealsohistologicallyindistinguishablebutareaquitedistinctdiseasethat usually remainslocalisedandhasamuchbetterprognosis. BonemarrowALamyloidosisAmyloidintissuesectionscanbeidentifiedbypositivestainingwith:1) Congored 2) Martiusscarletblue 3) Methenaminesilver 4) Prussianblue 5) Siriusred Correct answers 1, 5CongoredandSiriusredbothstainamyloidand,onexaminationbypolarisedlight,thereisapplegreen birefringence. Martius scarlet blue stains collagen, methenamine silver stains fungi and Prussianbluestainshaemosiderin.

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The mutational landscape of 18 investigated genes clearly separates four subtypes of myelodysplastic/myeloproliferative neoplasms

Cited by 41 publications

References 15 publications

<p>Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of <em>KRAS</em></p>

<p>Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of <em>KRAS</em></p>

SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms

Further discussion of the themes

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