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Acquired RhD mosaicism identifies fibrotic transformation of thrombopoietin receptor‐mutated essential thrombocythemia
Author(s) -
MontemayorGarcia Celina,
Coward Rebecca,
Albitar Maher,
Udani Rupa,
Jain Prachi,
Koklanaris Eleftheria,
Battiwalla Minoo,
Keel Siobán,
Klein Harvey G.,
Barrett A. John,
Ito Sawa
Publication year - 2017
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.14201
Subject(s) - loss of heterozygosity , biology , uniparental disomy , essential thrombocythemia , myeloid , myelofibrosis , immunology , population , allele , cancer research , genetics , bone marrow , gene , karyotype , chromosome , polycythemia vera , medicine , environmental health
BACKGROUND Acquired copy‐neutral loss of heterozygosity has been described in myeloid malignant progression with an otherwise normal karyotype. CASE REPORT A 65‐year‐old woman with MPL ‐mutated essential thrombocythemia and progression to myelofibrosis was noted upon routine pretransplant testing to have mixed field reactivity with anti‐D and an historic discrepancy in RhD type. The patient had never received transfusions or transplantation. RESULTS Gel immunoagglutination revealed group A red blood cells and a mixed‐field reaction for the D phenotype, with a predominant D‐negative population and a small subset of circulating red blood cells carrying the D antigen. Subsequent genomic microarray single nucleotide polymorphism profiling revealed copy‐neutral loss of heterozygosity of chromosome 1 p36.33‐p34.2, a known molecular mechanism underlying fibrotic progression of MPL ‐mutated essential thrombocythemia. The chromosomal region affected by this copy‐neutral loss of heterozygosity encompassed the RHD , RHCE , and MPL genes. We propose a model of chronological molecular events that is supported by RHD zygosity assays in peripheral lymphoid and myeloid‐derived cells. CONCLUSION Copy‐neutral loss of heterozygosity events that lead to clonal selection and myeloid malignant progression may also affect the expression of adjacent unrelated genes, including those encoding for blood group antigens. Detection of mixed‐field reactions and investigation of discrepant blood typing results are important for proper transfusion support of these patients and can provide useful surrogate markers of myeloproliferative disease progression.