Antigen receptor sequencing of paired bone marrow samples shows homogeneous distribution of acute lymphoblastic leukemia subclones
| Autor: | David van Zessen, Prisca M J Theunissen, Malek Faham, Jacques J.M. van Dongen, Vincent H.J. van der Velden, Andrew P. Stubbs, Christian M. Zwaan |
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| Přispěvatelé: | Immunology, Pathology, Pediatrics |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lymphoblastic Leukemia Bone Marrow Cells Biology Article Clonal Evolution 03 medical and health sciences 0302 clinical medicine Antigen Bone Marrow Antigen receptor medicine Humans Child Receptor Gene Gene Rearrangement Hematology Gene rearrangement Precursor Cell Lymphoblastic Leukemia-Lymphoma Acute Lymphoblastic Leukemia Molecular biology Peripheral blood Receptors Antigen 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Neoplastic Stem Cells Bone marrow |
| Zdroj: | Haematologica, 102(11), 1869-1877. Ferrata Storti Foundation Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2017.171454 |
| Popis: | In B-cell precursor acute lymphoblastic leukemia, the initial leukemic cells share the same antigen receptor gene rearrangements. However, due to ongoing rearrangement processes, leukemic cells with different gene rearrangement patterns can develop, resulting in subclone formation. We studied leukemic subclones and their distribution in the bone marrow and peripheral blood at diagnosis. Antigen receptor gene rearrangements (IGH, IGK, TRG, TRD, TRB) were analyzed by next-generation sequencing in seven paired bone marrow samples and five paired bone marrow-peripheral blood samples. Background-thresholds were defined, which enabled identification of leukemic gene rearrangements down to very low levels. Paired bone marrow analysis showed oligoclonality in all 7 patients and up to 34 leukemic clones per patient. Additional analysis of evolutionary-related IGH gene rearrangements revealed up to 171 leukemic clones per patient. Interestingly, overall 86% of all leukemic gene rearrangements, including small subclones, were present in both bone marrow samples (range per patient: 72–100%). Paired bone marrow-peripheral blood analysis showed that 83% of all leukemic gene rearrangements in bone marrow were also found in peripheral blood (range per patient: 81–100%). Remarkably, in the paired bone marrow samples and paired bone marrow-peripheral blood samples the vast majority of leukemic gene rearrangements had a similar frequency ( |
| Databáze: | OpenAIRE |
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