Session: 611. Leukemias: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Poster I
Of 99 samples from an unselected series from the Children’s Oncology Group trial AALL0932, we find that 92 of 98 samples have a clonal IGH gene rearrangement in pre-treatment samples. One sample failed at the outset during the DNA extraction step. Of the remaining 92 cases with pre-treatment VDJ or D-J rearrangements, 82 had evidence of on-going recombination in which VH replacement was identified in clones, each having conserved D-J rearrangements. The average number of clones was 192, but ranged from 1 to over 2000 unique sequences. In cases with VH replacement, an average of 4.12% of IGH sequences was made up of VH-replaced sequences. In post-treatment samples that were MRD positive, the predominant clone in pre-treatment samples was typically the most frequent clone. Clones consistent with VH replacement were found in 19 patients; in one patient, the only MRD detected was a single clone consistent with VH replacement at a level of ~1 in 1,000,000. In the other 18 post-treatment MRD positive cases, the dominant clone identified pre-treatment was also dominant post-treatment: on average, 3.2% of total IGH rearrangements matched the dominant clone post-treatment, while only 0.027% of IGH rearrangements were consistent with VH replacement of the major clone. Among pre-treatment samples in which VH replaced clones were detected, all VH replaced clones together were 12% as large as the dominant clone on average. Among post-treatment samples, VH replaced clones were on average 14% as large as the dominant clone, indicating little change in the relative proportions of the dominant clone and VH replaced sub-clones.
These findings together suggest that on-going rearrangement of the IGH locus is not likely to be important for clonal tumor evolution within the time frame of initial chemotherapy, as no substantial change in clonal diversity as assessed by IGH sequencing is evident. In other words, on-going rearrangement of IGH appears to be neutral with respect to therapy-induced selection of tumor clones that may represent early (day 29) relapse.
Disclosures: Emerson: Adaptive Biotechnologies: Employment, Equity Ownership. Sherwood: Adaptive Biotechnologies: Employment, Equity Ownership. Kirsch: Adaptive Biotechnologies: Employment, Equity Ownership. Carlson: Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties. Williamson: Adaptive Biotechnologies: Employment, Equity Ownership. Wood: Becton Dickinson and Company, NJ, USA: Research Funding. Robins: Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties.
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