TBL1XR1-JAK2: a novel fusion in a pediatric T cell acute lymphoblastic leukemia patient with increased absolute eosinophil count

Abstract

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) with any JAK2 gene fusion is rarely reported. Here, we report a case of T-ALL with a novel TBL1XR1-JAK2 gene fusion in a 5-year-old boy. His lab showed a high white blood cell count, mild anemia, moderate thrombocytopenia, and concurrently increased eosinophils (absolute eosinophil count: 4 × 10^9/L). Peripheral blood and bone marrow aspirate smears showed > 90% mononucleated blasts. Flow cytometry on peripheral blood revealed a large blast population positive for CD2, surface CD3 (< 25%), CD10 (50%), CD5, CD7, CD4, CD8, TdT, CD1a (60%), and CD45. Conventional karyotype analysis showed t(3;9)(q26;p24) and t(11;14)(p13;q11.2)/TCRD-LMO2. Next-generation sequencing (NGS) identified a novel TBL1XR1-JAK2 gene fusion in a sequencing depth of 180 × by RNAseq, FBXW7 R465H mutation, and loss of exons 2-3 of CDKN2A/B by DNAseq. Follow-up bone marrow aspirate on day-28 post-induction therapy revealed no morphologic evidence of residual leukemia. We believe that the TBL1XR1-JAK2 fusion may behave in a similar functional manner to the PCM1-JAK2 fusion gene and constitutes a new variant of this family and a potential target of tyrosine kinase inhibitor (TKI) therapy.

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

“…JAK2 alterations, including rearrangements and gain-of-function mutations, are associated with poor outcome within the Ph-like ALL subtype ( Roberts et al, 2014a ). It is unclear why JAK2 alterations are predominantly identified within B-ALL rather than T-cell ALL (T-ALL), although there have been rare reports in T-ALL ( Lacronique et al, 1997 ; Peeters et al, 1997 ; Cheng et al, 2017 ; Huang et al, 2020 ; Kaplan et al, 2021 ). JAK2 chromosomal rearrangements ( JAK2 r) which result in JAK2 fusion genes, correlate with some of the lowest survival rates within the Ph-like ALL subtype ( Figure 1 ) ( Roberts et al, 2014a ; Roberts K. G. et al, 2017 ).…”