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

Ribera, Jordi; Granada, Isabel; González, Teresa; Ciudad, Juana; Such, Esperanza; Calasanz, Marı́a José; Mercadal, Santiago; Coll, Rosa; González‐Campos, José; Tormo, Mar; García‐Cadenas, Irene; Gil, Cristina; Cervera, Marta; Barba, Pere; Costa, Dolors; Ayala, Rosa; Bermúdez, Arancha; Órfão, Alberto; Ribera, Josep‐María; Malignas, Programa para el Tratamiento de Hemopatias

doi:10.1111/bjh.17844

Cited by 5 publications

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The translocation t(1;19)(q23;p13) has been described as mostly unbalanced 156 , 32 – 34 . This is in accordance with the observation made in this study that in only 14 cases (33%) a reciprocal break site could be characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Historically, TCF3 :: PBX1 -positive leukemia has been associated with a poor prognosis, but this has been overcome by modern therapy regimens and TCF3 :: PBX1 currently defines a group of ALL patients with a good clinical outcome in childhood ALL 16 , 6 – 9 , although these patients appear to have an increased risk for CNS involvement at diagnosis 10 . The prognostic impact of TCF3 :: PBX1 in ALL in older patients (age > 15 years) is less well defined, and relatively few molecular-based and controversial data have been published in this area 11 – 15 . TCF3 :: PBX1 -positive ALL has been found to express the receptor tyrosine kinase ROR1, which may serve as a therapeutic target in the future 16 , 17 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment

Burmeister,

Gröger,

Gökbuget

et al. 2023

Sci Rep

View full text Add to dashboard Cite

The translocation t(1;19)(q23;p13) with the resulting chimeric TCF3::PBX1 gene is the third most prevalent recurrent chromosomal translocation in acute lymphoblastic leukemia and accounts for 3–5% of cases. The molecular background of this translocation has been incompletely studied, especially in adult cases. We characterized the chromosomal breakpoints of 49 patients with TCF3::PBX1 and the corresponding reciprocal PBX1::TCF3 breakpoints in 15 cases at the molecular level, thus providing an extensive molecular overview of this translocation in a well-defined study patient population. Breakpoints were found to be remarkably clustered not only in TCF3 but also in PBX1. No association with DNA repeats or putative cryptic recombination signal sequence sites was observed. A simplified detection method for breakpoint identification was developed and the feasibility of patient-specific chromosomal break sites as molecular markers for detecting measurable residual disease (MRD) was explored. A highly sensitive generic real-time PCR for MRD assessment using these breakpoint sequences was established that could serve as a useful alternative to the classical method utilizing rearranged immune gene loci. This study provides the first extensive molecular data set on the chromosomal breakpoints of the t(1;19)/TCF3::PBX1 aberration in adult ALL. Based on the obtained data a generic MRD method was developed that has several theoretical advantages, including an on average higher sensitivity and a greater stability of the molecular marker in the course of disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment

Burmeister,

Gröger,

Gökbuget

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes

Panda,

Rainchwar,

Singh

et al. 2024

Leukemia Research

View full text Add to dashboard Cite

Case of B-acute lymphoblastic leukaemia with t(1;19)(q23;p13.3)TCF3::PBX1and co-occurringCBLmutation in an elderly patient

Zabel,

Rebbe,

Vasef

et al. 2024

BMJ Case Rep

View full text Add to dashboard Cite

The t(1;19) (q23;p13)TCF3::PBX1is a well-described, recurring chromosomal abnormality in B-acute lymphoblastic leukaemia (B-ALL) that has historically been associated with a worse prognosis in paediatric patients. Gene expression profiling has demonstrated thatTCF3::PBX1results in a distinct subtype of B-ALL, leading to its recognition in the most recent WHO and ICC classifications. Though initially believed to be a poor prognostic sign in the adult population, emerging evidence suggests its presence may instead be intermediate or even favourable in B-ALL. However, adults withTCF3::PBX1are typically younger and often qualify for treatment with paediatric-inspired regimens. Thus, the prognostic significance in this population remains unclear. This translocation appears to be very rare in older adults with B-ALL and its predictive and prognostic nature in this population is unknown. Herein, we explore a case of this translocation occurring in a patient in her 70s. She initially presented to the emergency department with abdominal pain and thrombocytopenia and was subsequently diagnosed with B-ALL. In addition to t(1;19) (q23;p13), a pathologic mutation in theCBLgene was identified.CBLmutations have been implicated in cancer progression and are mostly described in paediatric B-ALL. She was treated with modified Ph-negative EWALL induction (Vincristine, Idarubicin, dexamethasone) and achieved a complete remission. However, she subsequently experienced an early relapse and was refractory to targeted therapy with blinatumomab. After treatment with inotuzumab ozogamicin, she achieved a second complete remission. Unfortunately, she then suffered a central nervous system (CNS) relapse and passed away from complications of her disease. This case serves as an example of the heterogeneous nature of B-ALL. It demonstrates that patients with ostensibly favourable prognostic factors may experience poor response rates to traditional chemotherapy as well as targeted salvage agents. It also illustrates the challenges of treating B-ALL in the elderly population.

show abstract

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

Cited by 5 publications

References 15 publications

Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment

Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment

Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes

Case of B-acute lymphoblastic leukaemia with t(1;19)(q23;p13.3)TCF3::PBX1and co-occurringCBLmutation in an elderly patient

Contact Info

Product

Resources

About