Antigen receptor sequencing of paired bone marrow samples shows homogeneous distribution of acute lymphoblastic leukemia subclones.

Antigen receptor sequencing of paired bone marrow samples shows homogeneous distribution of acute lymphoblastic leukemia subclones. Haematologica. 2017 Aug 31;: Authors: Theunissen PMJ, van Zessen D, Stubbs AP, Faham M, Zwaan M, van Dongen JJM, Van der Velden VHJ Abstract 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-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 seven 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-blood analysis showed that 83% of all leukemic gene rearrangements in bone...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research