Presenter Status
Fellow
Abstract Type
Case Report
Primary Mentor or Principal Investigator
Dr. Midhat Farooqi MD PhD
Presentation Type
Poster
Start Date
19-5-2026 12:00 PM
End Date
19-5-2026 1:00 PM
Abstract Text
Introduction
JAK2 rearrangements are recurrently observed (and correlate with some of the lowest survival rates) within Ph-like B-cell acute lymphoblastic leukemia but are very rare in T-cell Lymphoblastic Leukemia (T-ALL). Here we present a patient with pediatric T-ALL who was shown to have a TBL1XR1::JAK2 fusion by Optical Genome Mapping (OGM), which was further supported by long-read sequencing. This is only the second report of JAK2 fusing with TBL1XR1 in pediatric T-ALL.
Case Presentation
A 15-year-old male presented with intermittent fever, fatigue, and nausea for the past 7 days, bruising on extremities and chest, small nodules on the scalp, and prominent neck lymph nodes. He had an elevated White Blood Cell count of 108 x 109 cells/L and C-Reactive Protein at 7.0 mg/dL. Chest X-ray showed an anterior mediastinal mass.
Diagnostic Workup
Peripheral blood cells revealed frequent variably sized blasts with irregular nuclei and morphology consistent with lymphoblasts. The overall blast percentage was 62.5%. Based on clinical presentation and pathology results, the patient was diagnosed with T-ALL. Fluorescence in situ hybridization (FISH) was negative for KMT2A rearrangement and BCR::ABL1 gene fusion. Chromosome analysis showed a reciprocal translocation between chromosomes 3q and 9p [46,XY,t(3;9)(q25;p21)] in seven cells. Normal diploid cells were also present. Microarray analysis showed no evidence of this translocation, consistent with it being a balanced rearrangement, but did reveal copy neutral loss of heterozygosity of 9p encompassing biallelic loss of CDKN2A/CDKN2B and a loss within 4q25 containing LEF1. Paired tumor/normal cancer exome sequencing identified a Tier I variant in NOTCH1, c.4727T>A p.(Val1576Glu), at an estimated variant allele frequency (VAF) of 32% as well as Tier II variants in BCL11B, c.1349C>T p.(Thr450Met), and CDKN1B, c.165_253del p.(Ser56Argfs*39), at VAFs of 42% and 29%, respectively. OGM identified the translocation between chromosomes 3 and 9, which resulted in a TBL1XR1::JAK2 fusion. Rearrangement of the JAK2 locus was subsequently confirmed by FISH and a translocation involving TBL1XR1 and JAK2 was supported by long-read DNA sequencing (lrSeq).
Discussion and Conclusion
To the best of our knowledge there has only been one other pediatric T-ALL case reported with a TBL1XR1::JAK2 fusion. This fusion has been hypothesized to act similar to a PCM1::JAK2 fusion, which results in a chimeric protein with a constitutively active JAK2 kinase domain. This finding was not detectable via microarray or our standard T-ALL FISH panel, and although it was supported by chromosome analysis, without the use of OGM and/or lrSeq, this rare fusion would not have been found in this patient. Finally, this finding suggests that there may be an additional subgroup of pediatric patients with T-ALL who may benefit from JAK and/or tyrosine kinase inhibitors.
Rare TBL1XR1::JAK2 fusion in a patient with pediatric T-ALL identified by Optical Genome Mapping and long-read sequencing
Introduction
JAK2 rearrangements are recurrently observed (and correlate with some of the lowest survival rates) within Ph-like B-cell acute lymphoblastic leukemia but are very rare in T-cell Lymphoblastic Leukemia (T-ALL). Here we present a patient with pediatric T-ALL who was shown to have a TBL1XR1::JAK2 fusion by Optical Genome Mapping (OGM), which was further supported by long-read sequencing. This is only the second report of JAK2 fusing with TBL1XR1 in pediatric T-ALL.
Case Presentation
A 15-year-old male presented with intermittent fever, fatigue, and nausea for the past 7 days, bruising on extremities and chest, small nodules on the scalp, and prominent neck lymph nodes. He had an elevated White Blood Cell count of 108 x 109 cells/L and C-Reactive Protein at 7.0 mg/dL. Chest X-ray showed an anterior mediastinal mass.
Diagnostic Workup
Peripheral blood cells revealed frequent variably sized blasts with irregular nuclei and morphology consistent with lymphoblasts. The overall blast percentage was 62.5%. Based on clinical presentation and pathology results, the patient was diagnosed with T-ALL. Fluorescence in situ hybridization (FISH) was negative for KMT2A rearrangement and BCR::ABL1 gene fusion. Chromosome analysis showed a reciprocal translocation between chromosomes 3q and 9p [46,XY,t(3;9)(q25;p21)] in seven cells. Normal diploid cells were also present. Microarray analysis showed no evidence of this translocation, consistent with it being a balanced rearrangement, but did reveal copy neutral loss of heterozygosity of 9p encompassing biallelic loss of CDKN2A/CDKN2B and a loss within 4q25 containing LEF1. Paired tumor/normal cancer exome sequencing identified a Tier I variant in NOTCH1, c.4727T>A p.(Val1576Glu), at an estimated variant allele frequency (VAF) of 32% as well as Tier II variants in BCL11B, c.1349C>T p.(Thr450Met), and CDKN1B, c.165_253del p.(Ser56Argfs*39), at VAFs of 42% and 29%, respectively. OGM identified the translocation between chromosomes 3 and 9, which resulted in a TBL1XR1::JAK2 fusion. Rearrangement of the JAK2 locus was subsequently confirmed by FISH and a translocation involving TBL1XR1 and JAK2 was supported by long-read DNA sequencing (lrSeq).
Discussion and Conclusion
To the best of our knowledge there has only been one other pediatric T-ALL case reported with a TBL1XR1::JAK2 fusion. This fusion has been hypothesized to act similar to a PCM1::JAK2 fusion, which results in a chimeric protein with a constitutively active JAK2 kinase domain. This finding was not detectable via microarray or our standard T-ALL FISH panel, and although it was supported by chromosome analysis, without the use of OGM and/or lrSeq, this rare fusion would not have been found in this patient. Finally, this finding suggests that there may be an additional subgroup of pediatric patients with T-ALL who may benefit from JAK and/or tyrosine kinase inhibitors.
Comments
Poster Board Number : 2