22. Masked hypodiploid B-Cell Lymphoblastic Leukemia (B-ALL) characterized by SNP microarray in a Li Fraumeni syndrome patient with post therapy karyotype changes

Cases of B-ALL with chromosome counts of >60 and tetrasomic for chromosomes 6, 18, 21 and X are suspicious for “masked hypodiploidy” in that the theoretic hypodiploid stemline is present as a doubled clone only. To characterize and define these cases when FISH and chromosomes show no evidence of the hypodiploid clone, our laboratory utilizes the IlluminaⓇ Cyto-SNP 850K microarray to recognize the loss of heterozygosity (LOH) of the disomic chromosomes. We report an 18yo female with a known diagnosis of Li Fraumeni syndrome, referred to Cytogenetics with pancytopenia and circulating blasts. Cytogenetic results at diagnosis revealed three hyperdiploid clones with counts of 62-64, tetrasomy for X, 1, 6, 18, and 21, with additional trisomies and structural rearrangements including a derivative 17p with 11q. No evidence for monosomy was observed by FISH or chromosomes. Microarray results confirmed loss of heterozygosity (LOH) for those chromosomes present in 2 copies. Genes associated with low hypodiploid B-ALL include TP53, IKZF1 and RB1 which were present in 2 copies on the isodisomic chromosomes in this specimen. This patient was in remission for several months, but with reemergence of B-ALL, underwent CD19 directed CAR-T therapy which resulted in deep remission (by NGS-MRD). Recent surveillance studies showed a karyotype change to loss of 5q and TP53 by FISH and a dic(5;17)(q11.2;p11.2) consistent with MDS. Microarray studies confirm the MDS genetic findings and were negative for the masked hypodiploid findings present at diagnosis. This strategy has been useful to report chromosome results with confidence for cases of masked hypodiploidy that may have been otherwise misinterpreted.