Julie Feusiera, Rotem Fishel Ben-Kenanb, Denise Quigleya, Erica Andersenc, Bo Hongc
aARUP Laboratories, Salt Lake City, UT, United States; bDepartment of Hematology Oncology, Phoenix Children’s, Phoenix, AZ, United States; cARUP Laboratories and Pathology Department, University of Utah, Salt Lake City, UT, United States
High hyperdiploidy (HHD) is the most common cytogenetic abnormality in childhood B-cell acute lymphoblastic leukemia (B-ALL) and is generally associated with a favorable prognosis; however, 10-20% of patients with HHD B-ALL will ultimately relapse. Although certain trisomy combinations including chromosomes 4, 10, 17 and 18 have previously been reported to be associated with a superior outcome, recent studies redefined the relapse predictive chromosome trisomy combination. The role of clonal heterogeneity has become important for predicting outcomes in HHD B-ALL.
In this study, we describe the spectrum of recurrent and rare cytogenomic microarray (GMA) findings in 42 HHD B-ALL patients. Chromosome structural abnormalities were observed in 32/42 (76%) cases including focal deletions involving genes: CDKN2A, ATM, ARID2, ETV6, PTEN, BLNK and CREBBP; segmental gain involving 1q was the most recurrent structural aberration (n=13); deletions in 7p and 9p were seen in 4 and 3 cases respectively. Clonal diversity was observed in 13/42 (31%) cases; among these, 4/42 (10%) cases displayed subclones harboring additional aneuploidy. 16/42 (38%) cases showed copy-neutral loss-of-heterozygosity (CN-LOH) for one to seven chromosomes with chromosome 9 being the most frequently involved (6/16).
Clinically, chromosome analysis and fluorescence in-situ hybridization are routinely used at diagnosis to characterize the prognostic value of cytogenetic abnormalities in HHD B-ALL. However, these techniques may not detect small structural aberrations, CN-LOH or appreciate certain clonal diversity, which could be essential for precise risk stratification. GMA has proven to be a valuable test to enhance our understanding of the heterogeneous cytogenetic profile in HHD B-ALL.