Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia

Burmeister, Thomas; Gökbuget, Nicola; Schwartz, Stefan; Fischer, Lars; Hubert, Daniela; Sindram, Annette; Hoelzer, Dieter; Thiel, Eckhard

doi:10.3324/haematol.2009.011346

Cited by 73 publications

(46 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other factors that have recently acquired significance are persistence of minimal residual disease post-induction, molecular and genetic markers such as BCR-ABL, IKAROS and BAALC; and pharmacogenetics (7–9*). Table 1 shows prognostic markers that typically confer eligibility for alloHCT at first possible remission (10). …”

Section: Which Patients Should Be Transplanted?mentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Khaled

Thomas

Forman

2012

Current Opinion in Oncology

View full text Add to dashboard Cite

Purpose of review Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, for which treatment guidelines are still evolving. Allogeneic hematopoietic cell transplantation is a potentially curative therapeutic modality for ALL and this review describes recent studies and current practice patterns concerning the who, when, and how of alloHCT in the management of ALL. Recent findings Allogeneic stem cell transplantation is the treatment of choice for patients with ALL after first relapse, and is also recommended for high-risk patients in first complete remission (CR1). Minimal residual disease evaluation and monitoring is developing as an important prognostic factor and could guide physicians in determining which patients, especially those with standard risk, might require transplant. Tyrosine kinase inhibitor (TKI) therapy allows a much higher proportion of Philadelphia-chromosome-positive ALL patients to attain remission and proceed to transplant with improved results; post-transplant TKI maintainance therapy may also provide survival benefit. Reduced-intensity conditioning regimens are a reasonable alternative for patients who would otherwise be ineligible for transplant due to age or co-morbidity. Summary For patients with high-risk features, there is general agreement that allogeneic hematopoietic cell transplantation in CR1 is a potentially curative option; however, there is no consensus on early transplant for standard risk patients.

show abstract

Section: Which Patients Should Be Transplanted?mentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Khaled

Thomas

Forman

2012

Current Opinion in Oncology

View full text Add to dashboard Cite

show abstract

“…6 Most patients with TCF3-PBX1 BCP-ALL benefit from chemotherapy, however, the disease often recurs, at which point there are few effective treatment options. Targeted drugs may offer further opportunities for improving treatment outcome, and may also be associated with lower toxicity.…”

Section: Introductionmentioning

confidence: 99%

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

et al. 2016

View full text Add to dashboard Cite

TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug-sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL, whereas other drugs could be useful depending on the genetic context of individual patients.

show abstract

“…[2][3][4][5]13 Nevertheless, some recent long-term results revealed late relapses among patients with ETV6/RUNX1-positive ALL. 14,15 It has been hypothesized that a relapse is essentially a de novo ALL originating from a preleukemic stem cell. [16][17][18][19] This notion should be taken into account when considering the treatment options.…”

Section: Introductionmentioning

confidence: 99%

Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol

Gandemer

Chevret

Petit³

et al. 2012

Haematologica

View full text Add to dashboard Cite

The online version of this article has a Supplementary Appendix. BackgroundThe prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses. Design and MethodsAmong the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation. ResultsETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome. ConclusionsWe found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1-positive leukemia.

show abstract

Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia

Cited by 73 publications

References 41 publications

Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol

Contact Info

Product

Resources

About