Down Syndrome (DS) with B-Cell Acute Lymphoblastic Leukemia (B-ALL) versus Non-DS B-ALL in Children and Young Adults: Pathogenetic Differences 1Kaleigh Lindholm, MD; 1,2Liming Bao, PhD; 1,2Billie J Carstens; 1,3Xiayuan Liang, MD 1University of Colorado Anschutz Medical Campus; 2Colorado Cytogenetics Laboratory; 3 The Children's Hospital Colorado

The authors of this abstract have indicated that they have no conflicts of interest that relate to the content of this abstract. Background Results Down Syndrome (DS) is characterized by a constitutional extra copy of chromosome 21. Children with DS have an DS B-ALL Non-DS B-ALL p value increased incidence of acute leukemia, most commonly B-cell acute lymphoblastic leukemia (B-ALL). DS B-ALL is a Case # 31 87 distinct category and are treated with a chemotherapy regimen different from non-DS B-ALL based on Children’s Mean age 6.00 (1-21 y) 5.64 (10d-18y) 0.7410 Oncology Group. The 2016 WHO Classification of Hematologic Malignancies categorizes B-ALL into those Male:Female 21:10 35:42 0.0546 with and without recurrent genetic abnormalities, many of WBC (>=50k) 3/31 (9.68%) 13/87 (14.92%) 0.5560 which show significant prognostic indications. However, whether DS B-ALL patients and non-DS B-ALL share CSF+ 3/29 (10.34%) 26/84 (30.95%) 0.0832 pathogenetic features has not been well studied. We examined the pathogenetic landscape of both patient Mean S-phase 10.10 (1.60-22.40) 6.99 (0.40-20.00) 0.0194 populations to assess differences between DS B-ALL and non-DS B-ALL. ETV6-RUNX1 3/28 (10.71%) 12/84 (14.29%) 0.7577

Design BCR-ABL1 1/28 (3.57%) 4/84 (4.76%) 1.000 Between 2001 and 2019, 31 cases of newly diagnosed DS B-ALL were identified at our institution. We compared this Other recurrent cytogenetic 0/28 (0%) 24/84 (28.57%) 0.0004 group to newly diagnosed non-DS B-ALL in 2015 and 2016 abnormalities (87 cases). We analyzed age at diagnosis, M:F ratio, WBC (≥50k), CSF involvement, mean S-phase, recurrent Miscellaneous cytogenetic cytogenetic abnormalities (ETV6-RUNX1, BCR-ABL1, 16/28 (57.14%) 37/84 (44.05%) 0.2771 KMT2A-rearranged, TCF3-PBX1, IgH/IL3, iAMP21, abnormalities hyperdiploidy, and hyodiploidy), and other cytogenetic abnormalities. A p-value was calculated with a value of <0.05 considered statistically significant. DNA Analysis DS Patient DNA Analysis Non-DS Patient

Conclusion 1. Patients with DS have higher S-phase in their blasts than patients without DS suggesting that constitutional trisomy 21 may promote leukemic cell proliferation. 2. ETV6-RUNX1 and BCR-ABL1 fusions were seen equally in those with and without DS, but all other recurrent cytogenetic alterations are absent in DS patients. These findings suggest that constitutional trisomy 21 may selectively suppress certain recurrent cytogenetic abnormalities.