HAEM5:Myelodysplastic/myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis: Difference between revisions

Symptoms and clinical features are related to anemia, iron overload and thrombocytosis. Thrombocytemia manifests with thrombosis/hemorrhage. Differential diagnosis for thrombocytosis is Essential Thromocytopenia (ET) or reactive thrombocytosis.  

Ring sideroblasts are abnormal erythroid lineage precursors with increased mitochondrial iron deposits forming siderotic granules. A minimum of five distinct siderotic granules must be present, involving at least one third of the nuclear circumference.

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==Sites of Involvement==

No chromosomal rearrangements for MDS/MPN-RS-T

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

The presence of SF3B1 and JAK2 mutations is correlated with better prognosis and longer survival. Mutations in ASXL1, SETBP1 and EZH2 have negative prognostic significance <ref name=":2" /><ref name=":3" />. Abnormal karyotypes, although rare, correlate with very poor outcome <ref name=":3" />. Disease outcome: overall survival is better than in patients with MDS-RS-SLD, but worse than in patients with MPN-ET. There is low risk of converging to leukemic forms.<ref name=":0" /><ref name=":2" />

Treatment: transfusions, recombinant human erythropoietin for anemia. The use of Lenalidomide is controversial, while,  the use of Luspatercept- a novel erythroid maturation agent is not an established treatment option. Aspirin for thrombocytosis. Hydroxyurea is the preferred  cytoreductive agent <ref name=":2" />

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==Individual Region Genomic Gain / Loss / LOH==

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No genomic gain/loss for MDS/MPN-RS-T

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==Characteristic Chromosomal Patterns==

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No recurrent chromosomal aberrations for MDS/MPN-RS-T. However, abnormalities have been reported in 10% of patients. Trisomy 8 and loss of Y are the most common changes.<ref name=":3" />  

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==Gene Mutations (SNV / INDEL)==

The presence of concomitant  mutations in SF3B1 and JAK2 V617F support the diagnosis of MDS/MPN-RS-T; less commonly encountered are SF3B1 and CALR or SF3B1 and MPL <ref>{{Cite journal|last=S|first=Jeromin|last2=T|first2=Haferlach|last3=S|first3=Weissmann|last4=M|first4=Meggendorfer|last5=C|first5=Eder|last6=N|first6=Nadarajah|last7=T|first7=Alpermann|last8=A|first8=Kohlmann|last9=W|first9=Kern|date=2015|title=Refractory anemia with ring sideroblasts and marked thrombocytosis cases harbor mutations in SF3B1 or other spliceosome genes accompanied by JAK2V617F and ASXL1 mutations|url=https://pubmed.ncbi.nlm.nih.gov/25527566/|language=en|doi=10.3324/haematol.2014.119032|pmc=PMC4380732|pmid=25527566}}</ref><ref name=":3">{{Cite journal|last=L|first=Palomo|last2=M|first2=Meggendorfer|last3=S|first3=Hutter|last4=S|first4=Twardziok|last5=V|first5=Adema|last6=I|first6=Fuhrmann|last7=F|first7=Fuster-Tormo|last8=B|first8=Xicoy|last9=L|first9=Zamora|date=2020|title=Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/32573691/|language=en|pmid=32573691}}</ref>.

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==Epigenomic Alterations==

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SF3B1 gene mutations are present in over 80% of patients <ref name=":2" />. Somatic mutation in SF3B1 leads to abnormal ABCB7 protein, accumulation of mitochondrial iron and ineffective erythropoiesis, with formation of ring sideroblasts<ref>{{Cite journal|last=M|first=Cazzola|last2=M|first2=Rossi|last3=L|first3=Malcovati|date=2013|title=Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/23160465/|language=en|doi=10.1182/blood-2012-09-399725|pmc=PMC3790951|pmid=23160465}}</ref>. Mutations in JAK2 correlate with increased platelet count.<ref name=":3" />  

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==Genetic Diagnostic Testing Methods==