Kluk, Michael J.;
Abo, Ryan P.;
Brown, Ronald D.;
Kuo, Frank C.;
Dal Cin, Paola;
Pozdnyakova, Olga;
Morgan, Elizabeth A.;
Lindeman, Neal I.;
DeAngelo, Daniel J.;
Aster, Jon C.
Myeloid neoplasm demonstrating a STAT5B-RARA rearrangement and genetic alterations associated with all-trans retinoic acid resistance identified by a custom next-generation sequencing assay
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Medientyp:
E-Artikel
Titel:
Myeloid neoplasm demonstrating a STAT5B-RARA rearrangement and genetic alterations associated with all-trans retinoic acid resistance identified by a custom next-generation sequencing assay
Beteiligte:
Kluk, Michael J.;
Abo, Ryan P.;
Brown, Ronald D.;
Kuo, Frank C.;
Dal Cin, Paola;
Pozdnyakova, Olga;
Morgan, Elizabeth A.;
Lindeman, Neal I.;
DeAngelo, Daniel J.;
Aster, Jon C.
Beschreibung:
<jats:p>We describe the case of a patient presenting with several weeks of symptoms related to pancytopenia associated with a maturation arrest at the late promyelocyte/early myelocyte stage of granulocyte differentiation. A diagnosis of acute promyelocytic leukemia was considered, but the morphologic features were atypical for this entity and conventional tests for the presence of a <jats:italic>PML-RARA</jats:italic> fusion gene were negative. Additional analysis using a custom next-generation sequencing assay revealed a rearrangement producing a <jats:italic>STAT5B-RARA</jats:italic> fusion gene, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR) and supplementary cytogenetic studies, allowing the diagnosis of a morphologically atypical form of acute promyelocytic leukemia to be made. Analysis of the sequencing data permitted characterization of both chromosomal breakpoints and revealed two additional alterations, a small deletion in <jats:italic>RARA</jats:italic> exon 9 and a RARA R276W substitution, that have been linked to resistance to all-<jats:italic>trans</jats:italic> retinoic acid. This case highlights how next-generation sequencing can augment currently standard testing to establish diagnoses in difficult cases, and in doing so help guide selection of therapy.</jats:p>