Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors

Clonality testing for rearrangements in the complementarity-determining region 3 of the immunoglobulin heavy chain of B lymphocytes (B cell receptor) and the T cell receptor of T lymphocytes helps distinguish between clonal and non-clonal expansions of lymphocytes. There are rare reports of clonally...

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Autores principales: Stokol, Tracy, Nickerson, Gabrielle A., Shuman, Martha, Belcher, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449502/
https://www.ncbi.nlm.nih.gov/pubmed/28620611
http://dx.doi.org/10.3389/fvets.2017.00076
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author Stokol, Tracy
Nickerson, Gabrielle A.
Shuman, Martha
Belcher, Nicole
author_facet Stokol, Tracy
Nickerson, Gabrielle A.
Shuman, Martha
Belcher, Nicole
author_sort Stokol, Tracy
collection PubMed
description Clonality testing for rearrangements in the complementarity-determining region 3 of the immunoglobulin heavy chain of B lymphocytes (B cell receptor) and the T cell receptor of T lymphocytes helps distinguish between clonal and non-clonal expansions of lymphocytes. There are rare reports of clonally rearranged T and B cell receptors in dogs with acute myeloid leukemia (AML). Our objective was to determine the frequency of clonally rearranged T and B cell receptors in dogs with AML. Archived slides from historical cases of AML (from January 2010 to June 2013) and slides or liquid specimens [blood, bone marrow (BM), body cavity fluid, or tissue aspirates] from cases of AML diagnosed between June 2013 and February 2017 were used in the study. A diagnosis of AML was made on the basis of more than 20% immature neoplastic cells (“blasts”) in blood, BM, or extramedullary tissues, displaying features of myeloid differentiation. Myeloid differentiation was based on a combination of morphologic criteria, positive flow cytometric labeling for surface antigens typical of myeloid origin (e.g., CD11b, CD11c, CD14 with a general lack of expression of T or B cell markers), or positive cytochemical staining reactions for myeloid-associated enzymes (e.g., alkaline phosphatase, chloroacetate esterase). There were 63 cases of AML diagnosed during this period; however, slides or liquid specimens with sufficient DNA for testing were only obtained from 25 dogs. Affected dogs represented various breeds and were a median of 8 years old, with more male (64%) than female (36%) dogs. Common clinical signs were peripheral or internal lymphadenopathy (10/25 dogs, 40%) and hepatomegaly or splenomegaly (10/25 dogs combined, 40%). Typical hematologic findings were bi- or pancytopenia (23/25 dogs, 92%), with circulating blasts (21/25, 84%). Solitary clonal (4 B cell, 6 T cell) and biclonal (6 B and T cell) rearrangements in B or T cell receptors were found in 16 dogs (64%). Our results indicate that dogs with AML can have a high frequency of clonally rearranged T or B cell receptors, including biclonality, and clonality testing should not be used as a tool to distinguish between acute leukemia of myeloid or lymphoid origin.
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spelling pubmed-54495022017-06-15 Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors Stokol, Tracy Nickerson, Gabrielle A. Shuman, Martha Belcher, Nicole Front Vet Sci Veterinary Science Clonality testing for rearrangements in the complementarity-determining region 3 of the immunoglobulin heavy chain of B lymphocytes (B cell receptor) and the T cell receptor of T lymphocytes helps distinguish between clonal and non-clonal expansions of lymphocytes. There are rare reports of clonally rearranged T and B cell receptors in dogs with acute myeloid leukemia (AML). Our objective was to determine the frequency of clonally rearranged T and B cell receptors in dogs with AML. Archived slides from historical cases of AML (from January 2010 to June 2013) and slides or liquid specimens [blood, bone marrow (BM), body cavity fluid, or tissue aspirates] from cases of AML diagnosed between June 2013 and February 2017 were used in the study. A diagnosis of AML was made on the basis of more than 20% immature neoplastic cells (“blasts”) in blood, BM, or extramedullary tissues, displaying features of myeloid differentiation. Myeloid differentiation was based on a combination of morphologic criteria, positive flow cytometric labeling for surface antigens typical of myeloid origin (e.g., CD11b, CD11c, CD14 with a general lack of expression of T or B cell markers), or positive cytochemical staining reactions for myeloid-associated enzymes (e.g., alkaline phosphatase, chloroacetate esterase). There were 63 cases of AML diagnosed during this period; however, slides or liquid specimens with sufficient DNA for testing were only obtained from 25 dogs. Affected dogs represented various breeds and were a median of 8 years old, with more male (64%) than female (36%) dogs. Common clinical signs were peripheral or internal lymphadenopathy (10/25 dogs, 40%) and hepatomegaly or splenomegaly (10/25 dogs combined, 40%). Typical hematologic findings were bi- or pancytopenia (23/25 dogs, 92%), with circulating blasts (21/25, 84%). Solitary clonal (4 B cell, 6 T cell) and biclonal (6 B and T cell) rearrangements in B or T cell receptors were found in 16 dogs (64%). Our results indicate that dogs with AML can have a high frequency of clonally rearranged T or B cell receptors, including biclonality, and clonality testing should not be used as a tool to distinguish between acute leukemia of myeloid or lymphoid origin. Frontiers Media S.A. 2017-05-31 /pmc/articles/PMC5449502/ /pubmed/28620611 http://dx.doi.org/10.3389/fvets.2017.00076 Text en Copyright © 2017 Stokol, Nickerson, Shuman and Belcher. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Stokol, Tracy
Nickerson, Gabrielle A.
Shuman, Martha
Belcher, Nicole
Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors
title Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors
title_full Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors
title_fullStr Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors
title_full_unstemmed Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors
title_short Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors
title_sort dogs with acute myeloid leukemia have clonal rearrangements in t and b cell receptors
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449502/
https://www.ncbi.nlm.nih.gov/pubmed/28620611
http://dx.doi.org/10.3389/fvets.2017.00076
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