Contributions
Abstract: S799
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:00 - 08:15
Location: Room N103
Background
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for 10% to 15% of newly diagnosed cases of childhood acute lymphoblastic leukemia (ALL), arising from the malignant transformation of hematopoietic progenitors primed toward T cell development, as result of a multistep oncogenic process. However, since the prognostic significance of these genetic alterations in pediatric T-ALL is not clear, genetic basis which contributes aggressive phenotype or progression of pediatric T-ALL is still to be elucidated.
Aims
To discover driver genetic events, which involved in the aggressive phenotype of pediatric T-ALL and to identify its novel prognostic markers, we performed integrated genetic analysis in a large cohort of T-ALL case.
Methods
Our cohorts included samples from Tokyo Children’s Cancer Study Group (TCCSG) and Japan Association of Childhood Leukemia Study (JACLS). Whole transcriptome sequencing (WTS) was performed in 123 cases. Whole transcriptome sequencing (WTS) was performed in 123 cases.
Results
Representative recurrent fusion genes were as follows, SIL-TAL1 (n=25), MLL-ENL (n=5), PICALM-MLLT10 (n=5), and NUP214-ABL1 (n=2). Intriguingly, novel recurrent in-frame PU.1 fusions (STMN1-PU.1 n=2; TCF7-PU.1 n=5) were detected, and RT-PCR analysis in additional 60 cases revealed other 2 TCF7-PU.1 fusions. Thus, PU.1 fusions accounted for 4% of pediatric T-ALL/LBL. Expression data of WTS revealed cases with PU.1 fusion showed significantly higher expression of PU.1 compared to cases without PU.1 fusion, implicating that aberrant high expression of PU.1 involved in leukemogenesis.
Conclusion
PU.1 fusions expressing cells expanded and they remained at an immature stage, implicating a potential leukemogenic activity of these fusions. Not only the cases with PU.1 fusions, but also the cases with high PU.1 expression without fusions showed extremely poor prognosis, suggesting the prognostic value of aberrant PU.1 expression in pediatric T-ALL. Although it remains unclear, why cases with PU.1 fusions/high PU.1 expression have a poor prognosis, our results indicate that these cases are genetically distinct subgroup from other pediatric T-ALL.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): T cell acute lymphoblastic leukemia, Pediatric
Abstract: S799
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:00 - 08:15
Location: Room N103
Background
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for 10% to 15% of newly diagnosed cases of childhood acute lymphoblastic leukemia (ALL), arising from the malignant transformation of hematopoietic progenitors primed toward T cell development, as result of a multistep oncogenic process. However, since the prognostic significance of these genetic alterations in pediatric T-ALL is not clear, genetic basis which contributes aggressive phenotype or progression of pediatric T-ALL is still to be elucidated.
Aims
To discover driver genetic events, which involved in the aggressive phenotype of pediatric T-ALL and to identify its novel prognostic markers, we performed integrated genetic analysis in a large cohort of T-ALL case.
Methods
Our cohorts included samples from Tokyo Children’s Cancer Study Group (TCCSG) and Japan Association of Childhood Leukemia Study (JACLS). Whole transcriptome sequencing (WTS) was performed in 123 cases. Whole transcriptome sequencing (WTS) was performed in 123 cases.
Results
Representative recurrent fusion genes were as follows, SIL-TAL1 (n=25), MLL-ENL (n=5), PICALM-MLLT10 (n=5), and NUP214-ABL1 (n=2). Intriguingly, novel recurrent in-frame PU.1 fusions (STMN1-PU.1 n=2; TCF7-PU.1 n=5) were detected, and RT-PCR analysis in additional 60 cases revealed other 2 TCF7-PU.1 fusions. Thus, PU.1 fusions accounted for 4% of pediatric T-ALL/LBL. Expression data of WTS revealed cases with PU.1 fusion showed significantly higher expression of PU.1 compared to cases without PU.1 fusion, implicating that aberrant high expression of PU.1 involved in leukemogenesis.
Conclusion
PU.1 fusions expressing cells expanded and they remained at an immature stage, implicating a potential leukemogenic activity of these fusions. Not only the cases with PU.1 fusions, but also the cases with high PU.1 expression without fusions showed extremely poor prognosis, suggesting the prognostic value of aberrant PU.1 expression in pediatric T-ALL. Although it remains unclear, why cases with PU.1 fusions/high PU.1 expression have a poor prognosis, our results indicate that these cases are genetically distinct subgroup from other pediatric T-ALL.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): T cell acute lymphoblastic leukemia, Pediatric