Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia – a distinct subtype with favorable prognosis

Yılmaz, Musa; Kantarjian, Hagop M.; Toruner, Gokce; Yin, C. Cameron; Kanagal‐Shamanna, Rashmi; Cortes, Jorge; Issa, Ghayas C.; Short, Nicholas J.; Khoury, Joseph D.; Ravandi, Farhad; Kadia, Tapan M.; Konopleva, Marina; Wierda, William G.; Jain, Nitin; Estrov, Zeev; Sasaki, Koji; Pierce, Sherry; O’Brien, Susan

doi:10.1080/10428194.2020.1824071

Cited by 9 publications

(12 citation statements)

References 26 publications

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“…Age was a prognostic factor for patients with TCF3‐PBX1 , as shown in any ALL subtype. The median age of the patients with TCF3‐PBX1 in our present series (36 years) was older than that of other similar studies 2,3,5 and the frequency of alloHSCT was lower, 4 as alloHSCT indication was exclusively based on MRD‐status after induction and consolidation.…”

Section: Discussioncontrasting

confidence: 50%

Prognostic heterogeneity of adult B‐cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3‐PBX1 treated with measurable residual disease‐oriented protocols

et al. 2021

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The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).

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Section: Discussioncontrasting

confidence: 50%

Prognostic heterogeneity of adult B‐cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3‐PBX1 treated with measurable residual disease‐oriented protocols

et al. 2021

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“…Although initial reports linked the TCF3-PBX1 with poor prognosis, more recent reports demonstrate significantly improved outcomes with modern induction regimens in both children and adults. [39][40][41][42] Conversely, the TCF3-HLF rearrangement, resulting from t(17;19)(q22;p13), has a dismal prognosis. 43 A number of other gene partners have been reported, including ZNF384, NOL1 and TFPT, which may be cytogenetically cryptic.…”

Section: Tcf3 Rearrangementsmentioning

confidence: 99%

“…The most common fusion partner is PBX1 , manifested as t(1;19)(q23;p13·3), occurring in 4–6% of cases. Although initial reports linked the TCF3‐PBX1 with poor prognosis, more recent reports demonstrate significantly improved outcomes with modern induction regimens in both children and adults 39–42 . Conversely, the TCF3‐ HLF rearrangement, resulting from t(17;19)(q22;p13), has a dismal prognosis 43 .…”

Section: Lesions Evident With Cytogenetic Analysis: Numerical and Str...mentioning

confidence: 99%

B‐cell acute lymphoblastic leukaemia: recent discoveries in molecular pathology, their prognostic significance, and a review of the current classification

2021

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Summary Acute lymphoblastic leukaemia (ALL) remains a leading cause of non‐traumatic death in children, and the majority of adults diagnosed will succumb to the disease. Recent advances in molecular biology and bioinformatics have enabled more detailed genomic analysis and a better understanding of the molecular biology of ALL. A number of recurrent genomic drivers have recently been described, which not only aid in diagnosis and prognostication, but also may offer opportunities for specific therapeutic targeting. The present review summarises B‐ALL genomic pathology at diagnosis, including lesions detectable using traditional cytogenetic methods as well as those detected only through advanced molecular techniques.

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“…By contrast, the German Multicenter Therapy Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) did not find that the E2A‐PBX1 is a specific high‐risk entity in adult ALL 8 . Recently, the prognosis of adult ALL patients with t(1;19)(q23;p13) was reported to be improved by intensified regimens and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) 9 . Because of the rarity of this genotype, a consensus on the clinical and prognostic characteristics of adult E2A‐PBX1‐positive B‐ALL patients has not yet been reached.…”

Section: Introductionmentioning

confidence: 99%

“…8 Recently, the prognosis of adult ALL patients with t(1;19)(q23;p13) was reported to be improved by intensified regimens and allogeneic hematopoietic stem cell transplantation (allo-HSCT). 9 Because of the rarity of this genotype, a consensus on the clinical and prognostic characteristics of adult E2A-PBX1-positive B-ALL patients…”

mentioning

confidence: 99%

The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A‐PBX1: A 10‐year retrospective study

et al. 2021

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The clinical outcomes and genomic features of E2A‐PBX1 (TCF3‐PBX1)‐positive B‐cell acute lymphoblastic leukemia (B‐ALL) patients remain unclear. A total of 137 patients carrying E2A‐PBX1 among 3164 B‐ALL patients between 2009 and 2019 were retrospectively analyzed. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Age [DFS, p = 0.037; cumulative incidence of relapse (CIR), p = 0.005] and the level of minimal residual disease (MRD) after induction chemotherapy (OS, p = 0.020; DFS, p = 0.002; CIR, p = 0.006) were independent risk factors. In adolescents/adults, allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1) significantly improved the 5‐year prognosis (OS, p < 0.001; DFS, p < 0.001; CIR, p < 0.001). Haploidentical HSCT decreased the CIR compared with human leukocyte antigen‐matched HSCT in adolescents/adults (p = 0.017). Mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, nerve growth factor (NGF) signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children. Patients with multiple subclones at diagnosis tended to have unfavorable 3‐year prognoses (DFS, p = 0.010; CIR, p = 0.021). Leukemia clones with DNA repair gene mutations showed aggressive and treatment‐refractory phenotypes in this subtype of ALL. Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A‐PBX1‐positive B‐ALL outcomes. Allo‐HSCT, especially haploidentical HSCT, could improve the prognosis of adolescent/adult patients.

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Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia – a distinct subtype with favorable prognosis

Cited by 9 publications

References 26 publications

Prognostic heterogeneity of adult B‐cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3‐PBX1 treated with measurable residual disease‐oriented protocols

Prognostic heterogeneity of adult B‐cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3‐PBX1 treated with measurable residual disease‐oriented protocols

B‐cell acute lymphoblastic leukaemia: recent discoveries in molecular pathology, their prognostic significance, and a review of the current classification

The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A‐PBX1: A 10‐year retrospective study

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