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A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report

Introduction: Chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries, is a mature B-cell chronic lymphoproliferative disorder characterized by the accumulation of neoplastic CD5+ B lymphocytes, functionally incompetent and usually monoclonal in origin, in bone marrow, lymp...

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Autores principales: Cennamo, Michele, Sirocchi, Davide, Giudici, Carolina, Giagnacovo, Marzia, Petracco, Guido, Ferrario, Daniela, Garganigo, Simona, Papa, Angela, Veniani, Emanuela, Squizzato, Alessandro, Del Vecchio, Lucia, Patriarca, Carlo, Partenope, Michelarcangelo, Modena, Piergiorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299087/
https://www.ncbi.nlm.nih.gov/pubmed/37373803
http://dx.doi.org/10.3390/jcm12124110
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author Cennamo, Michele
Sirocchi, Davide
Giudici, Carolina
Giagnacovo, Marzia
Petracco, Guido
Ferrario, Daniela
Garganigo, Simona
Papa, Angela
Veniani, Emanuela
Squizzato, Alessandro
Del Vecchio, Lucia
Patriarca, Carlo
Partenope, Michelarcangelo
Modena, Piergiorgio
author_facet Cennamo, Michele
Sirocchi, Davide
Giudici, Carolina
Giagnacovo, Marzia
Petracco, Guido
Ferrario, Daniela
Garganigo, Simona
Papa, Angela
Veniani, Emanuela
Squizzato, Alessandro
Del Vecchio, Lucia
Patriarca, Carlo
Partenope, Michelarcangelo
Modena, Piergiorgio
author_sort Cennamo, Michele
collection PubMed
description Introduction: Chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries, is a mature B-cell chronic lymphoproliferative disorder characterized by the accumulation of neoplastic CD5+ B lymphocytes, functionally incompetent and usually monoclonal in origin, in bone marrow, lymph nodes and blood. Diagnosis occurs predominantly in elderly patients, with a median age reported between 67 and 72 years. CLL has a heterogeneous clinical course, which can vary from indolent to, less frequently, aggressive forms. Early-stage asymptomatic CLL patients do not require immediate therapeutic intervention, but only observation; treatment is necessary for patients with advanced disease or when “active disease” is observed. The most frequent autoimmune cytopenia (AIC) is autoimmune haemolytic anaemia (AHIA). The main mechanisms underlying the appearance of AIC in CLL are not fully elucidated, the predisposition of patients with CLL to suffering autoimmune complications is variable and autoimmune cytopenia can precede, be concurrent, or follow the diagnosis of CLL. Case presentation: A 74-year-old man was admitted to the emergency room following the finding of severe macrocytic anaemia during blood tests performed that same day, in particular the patient showed a profound asthenia dating back several months. The anamnesis was silent and the patient was not taking any medications. The blood examination showed an extremely high White Blood Cell count and findings of AIHA in CLL-type mature B-cell lymphoproliferative neoplasia. Genetic investigations: Conventional karyotyping was performed and it obtained a trisomy 8 and an unbalanced translocation between the short arm of chromosome 6 and the long arm of chromosome 11, concurrent with interstitial deletions in chromosomes 6q and 11q that could not be defined in detail. Molecular cytogenetics (FISH) analyses revealed Ataxia Telangiectasia Mutated (ATM) monoallelic deletion (with loss of ATM on derivative chromosome 11) and retained signals for TP53, 13q14 and centromere 12 FISH probes. TP53 and IGHV were not mutated. Array-CGH confirmed trisomy of the entire chromosome 8 and allowed us to resolve in detail the nature of the unbalanced translocation, revealing multiple regions of genomic losses on chromosomes 6 and 11. Discussion: The present case report is an unusual CLL case with complex karyotype and refinement of all breakpoints at the gene level by the genomic array. From a genetic point of view, the case under study presented several peculiarities. Conclusions: We report the genetic findings of a CLL patient with abrupt disease onset, so far responding properly to treatments despite the presence of distinct genetic adverse traits including ATM deletion, complex karyotype and chromosome 6q chromoanagenesis event. Our report confirms that interphase FISH alone is not able to provide an overview of the whole genomic landscape in selected CLL cases and that additional techniques are required to reach an appropriate cytogenetic stratification of patients.
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spelling pubmed-102990872023-06-28 A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report Cennamo, Michele Sirocchi, Davide Giudici, Carolina Giagnacovo, Marzia Petracco, Guido Ferrario, Daniela Garganigo, Simona Papa, Angela Veniani, Emanuela Squizzato, Alessandro Del Vecchio, Lucia Patriarca, Carlo Partenope, Michelarcangelo Modena, Piergiorgio J Clin Med Case Report Introduction: Chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries, is a mature B-cell chronic lymphoproliferative disorder characterized by the accumulation of neoplastic CD5+ B lymphocytes, functionally incompetent and usually monoclonal in origin, in bone marrow, lymph nodes and blood. Diagnosis occurs predominantly in elderly patients, with a median age reported between 67 and 72 years. CLL has a heterogeneous clinical course, which can vary from indolent to, less frequently, aggressive forms. Early-stage asymptomatic CLL patients do not require immediate therapeutic intervention, but only observation; treatment is necessary for patients with advanced disease or when “active disease” is observed. The most frequent autoimmune cytopenia (AIC) is autoimmune haemolytic anaemia (AHIA). The main mechanisms underlying the appearance of AIC in CLL are not fully elucidated, the predisposition of patients with CLL to suffering autoimmune complications is variable and autoimmune cytopenia can precede, be concurrent, or follow the diagnosis of CLL. Case presentation: A 74-year-old man was admitted to the emergency room following the finding of severe macrocytic anaemia during blood tests performed that same day, in particular the patient showed a profound asthenia dating back several months. The anamnesis was silent and the patient was not taking any medications. The blood examination showed an extremely high White Blood Cell count and findings of AIHA in CLL-type mature B-cell lymphoproliferative neoplasia. Genetic investigations: Conventional karyotyping was performed and it obtained a trisomy 8 and an unbalanced translocation between the short arm of chromosome 6 and the long arm of chromosome 11, concurrent with interstitial deletions in chromosomes 6q and 11q that could not be defined in detail. Molecular cytogenetics (FISH) analyses revealed Ataxia Telangiectasia Mutated (ATM) monoallelic deletion (with loss of ATM on derivative chromosome 11) and retained signals for TP53, 13q14 and centromere 12 FISH probes. TP53 and IGHV were not mutated. Array-CGH confirmed trisomy of the entire chromosome 8 and allowed us to resolve in detail the nature of the unbalanced translocation, revealing multiple regions of genomic losses on chromosomes 6 and 11. Discussion: The present case report is an unusual CLL case with complex karyotype and refinement of all breakpoints at the gene level by the genomic array. From a genetic point of view, the case under study presented several peculiarities. Conclusions: We report the genetic findings of a CLL patient with abrupt disease onset, so far responding properly to treatments despite the presence of distinct genetic adverse traits including ATM deletion, complex karyotype and chromosome 6q chromoanagenesis event. Our report confirms that interphase FISH alone is not able to provide an overview of the whole genomic landscape in selected CLL cases and that additional techniques are required to reach an appropriate cytogenetic stratification of patients. MDPI 2023-06-17 /pmc/articles/PMC10299087/ /pubmed/37373803 http://dx.doi.org/10.3390/jcm12124110 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Cennamo, Michele
Sirocchi, Davide
Giudici, Carolina
Giagnacovo, Marzia
Petracco, Guido
Ferrario, Daniela
Garganigo, Simona
Papa, Angela
Veniani, Emanuela
Squizzato, Alessandro
Del Vecchio, Lucia
Patriarca, Carlo
Partenope, Michelarcangelo
Modena, Piergiorgio
A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report
title A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report
title_full A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report
title_fullStr A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report
title_full_unstemmed A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report
title_short A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report
title_sort peculiar cll case with complex chromosome 6 rearrangements and refinement of all breakpoints at the gene level by genomic array: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299087/
https://www.ncbi.nlm.nih.gov/pubmed/37373803
http://dx.doi.org/10.3390/jcm12124110
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