Acute Promyelocytic Leukemia With Torque Teno Mini Virus::RARA Fusion: An Approach to Screening and Diagnosis.

Autor:	Tsai HK; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts., Sabbagh MF; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Montesion M; Foundation Medicine Inc, Boston, Massachusetts., Williams EA; Department of Pathology and Laboratory Medicine, University of Miami, Sylvester Comprehensive Cancer Center, and Jackson Memorial Hospitals, Miami, Florida; Foundation Medicine Inc, Boston, Massachusetts., Arbini A; Department of Pathology, NYU Grossman School of Medicine, New York City, New York., Boué DR; Department of Pathology & Laboratory Medicine, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio., Harris EM; Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts., Wachter F; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts., Grimmett L; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts., Place AE; Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts., Lucas F; Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts., Nardi V; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Kim AS; Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts., Brugnara C; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts., Degar B; Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts., Pollard J; Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts., Harris MH; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts., Bledsoe JR; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jacob.bledsoe@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2024 Jul; Vol. 37 (7), pp. 100509. Date of Electronic Publication: 2024 May 03.
DOI:	10.1016/j.modpat.2024.100509
Abstrakt:	Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely underrecognized due to the lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data. We describe a clinicopathologic approach and provide the necessary tools to screen and diagnose APL with TTMV::RARA using existing clinical DNA- or RNA-based NGS assays, which led to the identification of 4 cases, all without other known cytogenetic/molecular drivers. One was identified prospectively and 3 retrospectively, including 2 from custom automated screening of multiple data sets (50,257 cases of hematopoietic malignancy, including 4809 acute myeloid leukemia/myeloid sarcoma/APL cases). Two cases presented as myeloid sarcoma, including 1 with multiple relapses after acute myeloid leukemia-type chemotherapy and hematopoietic stem cell transplant. Two cases presented as leukemia, had a poor response to induction chemotherapy, but achieved remission upon reinduction (including all-trans retinoic acid in 1 case) and subsequent hematopoietic stem cell transplant. Neoplastic cells demonstrated features of APL including frequent azurophilic granules and dim/absent CD34 and HLA-DR expression. RARA rearrangement was not detected by karyotype or fluorescent in situ hybridization. Custom analysis of NGS fusion panel data identified TTMV::RARA rearrangements and, in the prospectively identified case, facilitated monitoring in sequential bone marrow samples. APL with TTMV::RARA is a rare leukemia with a high rate of treatment failure in described cases. The diagnosis should be considered in leukemias with features of APL that lack detectable RARA fusions and other drivers, and may be confirmed by appropriate NGS tests with custom informatics. Incorporation of all-trans retinoic acid may have a role in treatment but requires accurate recognition of the fusion for appropriate classification as APL. (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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