TBL1XR1-JAK2: a novel fusion in a pediatric T cell acute lymphoblastic leukemia patient with increased absolute eosinoph
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CASE REPORT
TBL1XR1-JAK2: a novel fusion in a pediatric T cell acute lymphoblastic leukemia patient with increased absolute eosinophil count Xiaoyan Huang 1 & Mahmut Celiker 2 & Ludovico Guarini 2 & Smita Patel 3 & Ning Neil Chen 1,3 Received: 11 May 2020 / Accepted: 23 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) with any JAK2 gene fusion is rarely reported. Here, we report a case of TALL 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. Keywords T-ALL/LBL . TBL1XR1-JAK2 gene fusion . Tyrosine kinase inhibitor
Introduction T cell acute lymphoblastic leukemia/lymphoma (T-ALL/ LBL) is an aggressive malignancy of early T cell progenitors, involving bone marrow and blood (T-ALL) or presenting with primary involvement in the thymus, lymph node, or extranodal site (T-LBL). It accounts for about 10–15% pediatric ALL cases with a predominance in male adolescents [1]. T-ALL/LBL in childhood is generally considered a higherrisk disease for presenting with high-risk features at diagnosis, such as older age and higher white blood cell count [2].
* Ning Neil Chen [email protected] 1
Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA
2
Department of Pediatric Hematology and Oncology, Maimonides Medical Center, Brooklyn, NY 11219, USA
3
Department of Pathology, Maimonides Medical Center, Brooklyn, NY 11219, USA
Common genomic alterations in T-ALL/LBL include the activating mutation of the NOTCH1 signaling pathway, inactivating mutation of FBXW7 signaling, and deletion or methylation of CDKN2A and CDKN2B [3]. Constitutional activation of JAK-STAT results from an activating mutation of JAK1 and JAK3 and is found in 10% of T-ALL/LBL patients [3]. JAK2 gene fusions have been reported in pediatric TALL/LBL cases (see Table 1). To date, more than thirty JAK2 fusion variants affecting TEL(ETV6), PCM1, TPM3, CD99, MYH9, BCR, SSBP2, STRN3, PAX5, and others have been described
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