PMID- 35119131 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20220731 IS - 1096-8652 (Electronic) IS - 0361-8609 (Print) IS - 0361-8609 (Linking) VI - 97 IP - 5 DP - 2022 May TI - Optimizing the diagnostic workflow for acute lymphoblastic leukemia by optical genome mapping. PG - 548-561 LID - 10.1002/ajh.26487 [doi] AB - Acute lymphoblastic leukemia (ALL) is a malignancy that can be subdivided into distinct entities based on clinical, immunophenotypic and genomic features, including mutations, structural variants (SVs), and copy number alterations (CNA). Chromosome banding analysis (CBA) and Fluorescent In-Situ Hybridization (FISH) together with Multiple Ligation-dependent Probe Amplification (MLPA), array and PCR-based methods form the backbone of routine diagnostics. This approach is labor-intensive, time-consuming and costly. New molecular technologies now exist that can detect SVs and CNAs in one test. Here we apply one such technology, optical genome mapping (OGM), to the diagnostic work-up of 41 ALL cases. Compared to our standard testing pathway, OGM identified all recurrent CNAs and SVs as well as additional recurrent SVs and the resulting fusion genes. Based on the genomic profile obtained by OGM, 32 patients could be assigned to one of the major cytogenetic risk groups compared to 23 with the standard approach. The latter identified 24/34 recurrent chromosomal abnormalities, while OGM identified 33/34, misinterpreting only 1 case with low hypodiploidy. The results of MLPA were concordant in 100% of cases. Overall, there was excellent concordance between the results. OGM increased the detection rate and cytogenetic resolution, and abrogated the need for cascade testing, resulting in reduced turnaround times. OGM also provided opportunities for better patient stratification and accurate treatment options. However, for comprehensive cytogenomic testing, OGM still needs to be complemented with CBA or SNP-array to detect ploidy changes and with BCR::ABL1 FISH to assign patients as soon as possible to targeted therapy. CI - (c) 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC. FAU - Rack, Katrina AU - Rack K AD - Laboratory for the Cytogenetic and Molecular Diagnosis of Hematological Malignancies, Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium. FAU - De Bie, Jolien AU - De Bie J AD - Laboratory for the Cytogenetic and Molecular Diagnosis of Hematological Malignancies, Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium. AD - Laboratory for the Molecular Biology of Leukemia, KU Leuven, Leuven, Belgium. FAU - Ameye, Genevieve AU - Ameye G AD - Laboratory for the Cytogenetic and Molecular Diagnosis of Hematological Malignancies, Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium. FAU - Gielen, Olga AU - Gielen O AD - Laboratory for the Molecular Biology of Leukemia, KU Leuven, Leuven, Belgium. AD - Centre for Cancer Biology, Flemish Institute for Biotechnology (VIB), Leuven, Belgium. FAU - Demeyer, Sofie AU - Demeyer S AD - Laboratory for the Molecular Biology of Leukemia, KU Leuven, Leuven, Belgium. AD - Centre for Cancer Biology, Flemish Institute for Biotechnology (VIB), Leuven, Belgium. FAU - Cools, Jan AU - Cools J AD - Laboratory for the Molecular Biology of Leukemia, KU Leuven, Leuven, Belgium. AD - Centre for Cancer Biology, Flemish Institute for Biotechnology (VIB), Leuven, Belgium. AD - Leuvens Kanker Instituut (LKI), KU Leuven - University Hospitals Leuven, Leuven, Belgium. FAU - De Keersmaecker, Kim AU - De Keersmaecker K AD - Leuvens Kanker Instituut (LKI), KU Leuven - University Hospitals Leuven, Leuven, Belgium. AD - Department of Oncology, KU Leuven, Leuven, Belgium. FAU - Vermeesch, Joris R AU - Vermeesch JR AD - Department of Human Genetics, KU Leuven, Leuven, Belgium. AD - Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium. FAU - Maertens, Johan AU - Maertens J AD - Department of Hematology, University Hospitals Leuven, Leuven, Belgium. FAU - Segers, Heidi AU - Segers H AD - Leuvens Kanker Instituut (LKI), KU Leuven - University Hospitals Leuven, Leuven, Belgium. AD - Department of Pediatric Oncology-Hematology, University Hospitals Leuven, Leuven, Belgium. FAU - Michaux, Lucienne AU - Michaux L AD - Laboratory for the Cytogenetic and Molecular Diagnosis of Hematological Malignancies, Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium. FAU - Dewaele, Barbara AU - Dewaele B AUID- ORCID: 0000-0002-1183-5228 AD - Laboratory for the Cytogenetic and Molecular Diagnosis of Hematological Malignancies, Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium. LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20220309 PL - United States TA - Am J Hematol JT - American journal of hematology JID - 7610369 SB - IM EIN - Am J Hematol. 2022 May 10;:. PMID: 35535476 MH - *Chromosome Aberrations MH - Chromosome Mapping/methods MH - DNA Copy Number Variations MH - Humans MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics MH - Workflow PMC - PMC9314940 COIS- The authors declare that there is no conflict of interest. EDAT- 2022/02/05 06:00 MHDA- 2022/04/08 06:00 PMCR- 2022/07/26 CRDT- 2022/02/04 08:42 PHST- 2022/01/28 00:00 [revised] PHST- 2021/10/16 00:00 [received] PHST- 2022/02/01 00:00 [accepted] PHST- 2022/02/05 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2022/02/04 08:42 [entrez] PHST- 2022/07/26 00:00 [pmc-release] AID - AJH26487 [pii] AID - 10.1002/ajh.26487 [doi] PST - ppublish SO - Am J Hematol. 2022 May;97(5):548-561. doi: 10.1002/ajh.26487. Epub 2022 Mar 9.