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dc.contributor.authorSelove, William
dc.contributor.authorDresser, Karen A.
dc.contributor.authorChen, Benjamin
dc.date2022-08-11T08:08:15.000
dc.date.accessioned2022-08-23T15:47:59Z
dc.date.available2022-08-23T15:47:59Z
dc.date.issued2016-05-20
dc.date.submitted2016-07-18
dc.identifier.doi10.13028/paq3-y933
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28113
dc.description.abstractIntroduction Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm that has been associated with a number of genetic mutations, most commonly TET2 mutations in up to 50-60% of cases. Mutations in epigenetic genes such as TET2 are known to disrupt the conversion of 5-methycytosine to 5-hydroxymethylcytosine (5hmC), contributing to oncogenesis. We hypothesized that CMML cases would exhibit decreased 5hmC expression, reflecting the propensity for TET2 mutations in CMML. We also sought to determine whether 5hmC IHC status reflected disease severity in terms of progression to AML and overall patient survival. Methods Thirty-five cases of CMML from between 1/2006 and 12/2014 were identified from the pathology archives at UMass, under an IRB-approved protocol. IHC was performed on FFPE bone marrow biopsy specimens with an anti-5hmC antibody. Staining was scored based on intensity of nuclear staining: 0 (neg) to 3+ (strong); and proportion of cells staining: 0 ( < 1%), 1 (1-25%), 2 (26-50%), 3 (51-75%), 4 ( > 76%). A combined product score was calculated yielding scores of 0-12. Correlation to clinical parameters (age, blast count, progression to AML, and overall patient survival) was investigated. Results 60% (21/35) of CMML cases showed low expression of 5hmc (combined score < =4). This loss of 5hmC expression correlated significantly with poorer overall survival in Kaplan-Meier curves (p=0.0287). There was no significant correlation between 5hmC score and patient age, blast count, or AML progression. Conclusion IHC detection of 5hmC in CMML is significantly correlated with patient overall survival and could potentially be utilized as a prognostic biomarker. Loss of 5hmC expression likely reflects mutations to epigenetic pathways and could be useful in guiding treatment with hypomethylating agents.
dc.formatyoutube
dc.language.isoen_US
dc.rightsCopyright the Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectChronic Myelomonocytic Leukemia
dc.subjectTET2 mutations
dc.subjectNeoplasms
dc.subjectPathology
dc.title5-Hyroxymethylcytosine Immunohistochemical Staining Correlates with Overall Survival in Patients with Chronic Myelomonocytic Leukemia
dc.typePoster Abstract
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1441&amp;context=cts_retreat&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cts_retreat/2016/posters/76
dc.identifier.contextkey8844718
refterms.dateFOA2022-08-23T15:47:59Z
html.description.abstract<p>Introduction Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm that has been associated with a number of genetic mutations, most commonly TET2 mutations in up to 50-60% of cases. Mutations in epigenetic genes such as TET2 are known to disrupt the conversion of 5-methycytosine to 5-hydroxymethylcytosine (5hmC), contributing to oncogenesis. We hypothesized that CMML cases would exhibit decreased 5hmC expression, reflecting the propensity for TET2 mutations in CMML. We also sought to determine whether 5hmC IHC status reflected disease severity in terms of progression to AML and overall patient survival.</p> <p>Methods Thirty-five cases of CMML from between 1/2006 and 12/2014 were identified from the pathology archives at UMass, under an IRB-approved protocol. IHC was performed on FFPE bone marrow biopsy specimens with an anti-5hmC antibody. Staining was scored based on intensity of nuclear staining: 0 (neg) to 3+ (strong); and proportion of cells staining: 0 ( < 1%), 1 (1-25%), 2 (26-50%), 3 (51-75%), 4 ( > 76%). A combined product score was calculated yielding scores of 0-12. Correlation to clinical parameters (age, blast count, progression to AML, and overall patient survival) was investigated.</p> <p>Results 60% (21/35) of CMML cases showed low expression of 5hmc (combined score < =4). This loss of 5hmC expression correlated significantly with poorer overall survival in Kaplan-Meier curves (p=0.0287). There was no significant correlation between 5hmC score and patient age, blast count, or AML progression.</p> <p>Conclusion IHC detection of 5hmC in CMML is significantly correlated with patient overall survival and could potentially be utilized as a prognostic biomarker. Loss of 5hmC expression likely reflects mutations to epigenetic pathways and could be useful in guiding treatment with hypomethylating agents.</p>
dc.identifier.submissionpathcts_retreat/2016/posters/76


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