19. High resolution cytogenomic analysis reveals characterizing abnormalities in APL-like leukemia

We report comprehensive characterization of cytogenomic findings from a bone marrow sample with suspected acute promyelocytic leukemia (APL) based on morphology and immunophenotype. Fluorescence in situ hybridization (FISH) and chromosome banding analysis (CBA) were negative for canonical PML::RARA and variant RARA translocations. PCR was negative for increased PML::RARA transcripts. CBA analysis detected loss of 5q, 17p as well as double minutes (dmin). To further rule out other retinoic acid receptor (RAR) partners, such as RARB, RARG, and identify the dmin, we employed genome-wide structural variant analysis (gSVA) using optical genome mapping. Interestingly, gSVA unmasked the dmin to be of MYC origin with ∼44 copies; this abnormality has been reported in APL-like leukemia and explained the immunophenotype. gSVA also identified loss of TP53, loss of chromosomes 1, 2, 8, 9 (includes CDKN2A), 10, and 11 along with gains of chromosomes 3, 6, 7, and 15 as separate clonal events.

No additional RAR partner translocations were observed. gSVA also showed a complex translocation, adjacent to 3Mb euploid region of 17p, in a rearrangement with chromosome 5, fusing genes DMGDH-AKAP10. As part of the testing algorithm, heme exome-based panel analysis detected a Tier I deleterious variant in TP53 (p.S241C). A 4-month follow up bone marrow again analyzed by gSVA, post induction therapy, showed a reduction in MYC amplification (∼4 copies). This work helped explain the APL-like phenotype for this rare leukemia in an initially emergent situation, provided a marker for follow-up testing, and merits integrated genomic analysis of similar cases.