Hyperdiploidy with greater than 50 chromosomes is usually associated with favorable prognosis in pediatric acute lymphoblastic leukemia (ALL), whereas hypodiploidy with ≤43 chromosomes is associated with extremely poor prognosis. Sometimes, hypodiploidy is “masked” and patients do not have a karyotypically visible clone with ≤43 chromosomes. Instead, their abnormal karyotypes contain 50–78 or more chromosomes from doubling of previously hypodiploid cells. When the hypodiploid and doubled hyperdiploid clones are both present, patients can be identified by traditional test methods [karyotype, DNA Index (DI), fluorescence in situ hybridization (FISH)], but the incidence of masked hypodiploid cases in which only the doubled clone is visible is unknown. We analyzed 7013 patients with B-ALL enrolled in COG AALL03B1 (2003–2011) for whom chromosome studies were available. Of 115 patients with hypodiploidy (25–39 chromosomes), karyotypes of 40 showed only the hypodiploid clone, 47 showed mosaicism with both hypodiploid and hyperdiploid (doubled) karyotypes, and 28 with masked hypodiploidy showed only a hyperdiploid (doubled) clone. Unique karyotypic signatures were identified, and widespread loss of heterozygosity (LOH) was seen in the microsatellite panel for all patients with masked hypodiploidy. An increased awareness of the unusual karyotypic profile associated with a doubled hypodiploid clone and coordinated use of DI, FISH, and LOH studies when indicated can identify patients with masked hypodiploidy and allow appropriate treatment selection.
Bibliographical noteFunding Information:
Supported by grants U10 CA98543 and U10 CA180886 from the National Institutes of Health .
Supported by grants U10 CA98543 and U10 CA180886 from the National Institutes of Health. The authors thank the patients and parents who participated in the AALL03B1 protocol and the cytogeneticists at the COG-approved laboratories who contributed to this study. MLL is the UCSF Benioff Chair of Children's Health and Deborah and Arthur Ablin Endowed Chair in Pediatric Molecular Oncology. EAR is a KiDS of NYU Foundation Professor at NYU Langone Health. SPH is the Jeffrey E. Perelman Distinguished Chair in the Department of Pediatrics at the Children's Hospital of Philadelphia.
© 2019 Elsevier Inc.