91. Atypical BCR::ABL1 rearrangements identified by optical genome mapping in patients with chronic myeloid leukemia

Aly Abdelkareem

Trilochan Sahoo

Dr. Trilochan Sahoo is a board-certified cytogeneticist and currently Clinical Laboratory Director at Bionano Laboratories, San Diego, CA. Following ABMGG fellowship training, he served as a Laboratory Director at Baylor College of Medicine, Signature Genomics, Quest Diagnostics, Combimatrix and most recently at Invitae. His work in cytogenetics included implementation of chromosomal microarrays in clinical genetics and discovery of a number of syndromic and non-syndromic genomic disorders. His interests include technology development, validation and implementation in the areas of prenatal, postnatal, reproductive genetics and more recently, utilizing Optical Genome Mapping as a diagnostic tool in constitutional cytogenetics and hematologic cancers.


Trilochan Sahoo, Alex Hastie, Allison Ortega, Anusha Mylavarapu, Beth Matthews, Jen Hauenstein, Alka Chaubey

Bionano Laboratories, San Diego, CA, United States

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by characteristic 9;22 translocation leading to the BCR::ABL1 fusion gene on the so-called Philadelphia chromosome. Identification of the common translocation is by conventional cytogenetic methods; detection of rarer and atypical variants of the  BCR::ABL1 fusion gene are challenging and often require multiple techniques. Here  two cases with CML are presented, each with atypical BCR::ABL1 rearrangements identified with high sensitivity and specificity by optical genome mapping (OGM).

In the first case (26-year-old male with CML),  OGM performed on a bone marrow aspirate (BMA) specimen revealed an inversion at 22q11.21q11.23 with a break within BCR and concurrent insertional translocation of  9q34.12q34.13 segment (with a break within ABL1) at 22q11.23 in an inverted manner and in transcriptional orientation that is expected to result in a BCR::ABL1 gene fusion. Case 2 was a 32-year-old male, OGM performed on BMA  detected a reciprocal translocation t(9;22)(q34.12;q11.23). This translocation disrupts the BCR gene on 22q within the major breakpoint cluster; however, the breakpoint on 9q is immediately upstream of the ABL1 gene. This rare translocation variant is predicted to result in an atypical but pathogenic BCR::ABL1 gene fusion. Accurate detection of atypical and rare variants of commonly detected pathogenic translocations are critical to accurate diagnosis and design of the appropriate follow-up test and monitoring. These two cases highlight the high sensitivity of OGM to resolve atypical rearrangements not amenable by current cytogenetic methods.