The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia

Abstract

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome-like BALL (Ph-like BALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like BALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like BALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between BALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

GA4GH: International policies and standards for data sharing across genomic research and healthcare

“… 54 – 56 Characterizing a cancer by sequencing a patient’s tumor genome alongside their germline genome has resulted in profound insights into molecular mechanisms of malignant transformation and discovery of potential therapeutic targets. 57 , 58 Tumor/normal sequencing has demonstrated applications in disease monitoring 59 as well as diagnosis, 60 prognosis, 61 and therapeutic response prediction, 62 both at initial presentation 63 and disease recurrence. 64 …”