Mantle cell lymphoma-variant Richter syndrome: Detailed molecular-cytogenetic and backtracking analysis reveals slow evolution of a pre-MCL clone in parallel with CLL over several years
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu kazuistiky, časopisecké články
PubMed
27407063
DOI
10.1002/ijc.30263
Knihovny.cz E-zdroje
- Klíčová slova
- Richteŕs transformation, chronic lymphocytic leukemia, clonal evolution, mantle cell lymphoma, transforming genes,
- MeSH
- chronická lymfatická leukemie genetika metabolismus patologie MeSH
- difúzní velkobuněčný B-lymfom genetika metabolismus patologie MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 11 MeSH
- lidské chromozomy, pár 14 MeSH
- lymfom z plášťových buněk genetika metabolismus patologie MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorový supresorový protein p53 genetika metabolismus MeSH
- translokace genetická MeSH
- ztráta heterozygozity MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- nádorové biomarkery MeSH
- nádorový supresorový protein p53 MeSH
- TP53 protein, human MeSH Prohlížeč
Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-based second-line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole-exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of ATM gene or emergence of TP53, CREBBP, NUP214, FUBP1 and SF3B1 gene mutations. Similarly, gene expression analysis revealed vast differences between the MCL and CLL transcriptome, including overexpression of cyclin D1, downregulation of cyclins D2 and D3, or downregulation of IL4R in the MCL clone. Backtracking analysis using quantitative PCR specifically detecting an MCL-restricted focal deletion of TP53 revealed that the pre-MCL clone appeared in the bone marrow and peripheral blood of the patient approximately 4 years before the clinical manifestation of MCL. Both molecular cytogenetic and sequencing data support the hypothesis of a slow development of the pre-MCL clone in parallel to CLL over several years, and thereby exclude the possibility that the transformation event occurred at the stage of the CLL relapse clone by mere t(11;14)(q13;q32) acquisition.
Childhood Leukemia Investigation Prague Faculty Hospital Motol Prague Prague Czech Republic
Department of Hematology Charles University General Hospital Prague Prague Czech Republic
Department of Pathology Charles University General Hospital Prague Prague Czech Republic
Synlab Genetics Department of Cytogenetics Prague Czech Republic
Citace poskytuje Crossref.org
Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma
