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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
Utilization of RT-PCR and Optical Genome Mapping in Acute Promyelocytic Leukemia with Cryptic PML::RARA
Giby V George1, Murad Elsadawi2, Andrew G Evans1
1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Background:
Acute promyelocytic leukemia (APL) is characterized by abnormal promyelocytes and t(15;17)(q24;q21) PML::RARA. Rarely, patients may have cryptic or variant rearrangements. All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) is largely curative provided that the diagnosis is established early.
Methods:
We present the case of a 36-year-old male who presented with features concerning for disseminated intravascular coagulation. Although the initial diagnostic work-up, including pathology and flow cytometry evaluation, suggested a diagnosis of APL, karyotype and fluorescence in situ hybridization (FISH), using the PML/RARA dual fusion and RARA breakapart probes, were negative. We performed real-time polymerase chain reaction (RT-PCR) and optical genome mapping (OGM) to further confirm the clinicopathological findings.
Results:
RT-PCR revealed a cryptic PML::RARA fusion transcript. OGM further confirmed the nature and orientation of a cryptic rearrangement with an insertion of RARA into PML at intron 3 (bcr3). In light of these findings, we performed a systematic literature review to understand the prevalence, diagnosis, and prognosis of APL with cryptic PML::RARA rearrangements.
Conclusions:
This case, in conjunction with the results of our systematic literature review, highlights the importance of performing confirmatory testing in FISH-negative cases of suspected APL to enable prompt diagnosis and appropriate treatment.
