EARLY T-CELL PRECURSOR LEUKEMIA: A SUBTYPE OF VERY HIGH-RISK ACUTE LYMPHOBLASTIC LEUKEMIA IDENTIFIED IN TWO INDEPENDENT COHORTS
By E. Coustan-Smith, C. Mullighan, M. Onciu, F. Behm, S. Raimondi, Deqing Pei, Cheng Cheng, X. Su, J. Rubnitz, G. Basso and 4 more. The Lancet Oncology, 2009
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Background Approximately one-fifth of children with acute T-lymphoblastic leukemia (T-ALL) succumb to the disease, suggesting unrecognized biologic heterogeneity that may contribute to drug resistance. We hypothesized that T-ALL originating from early T-cell precursors (ETPs), a recently defined subset of thymocytes that retain stem cell-like features, would respond poorly to lymphoid-cell directed therapy. We studied leukemic cells, collected at diagnosis, to identify cases with ETP features and determine their clinical outcome. Methods Leukemic cells from 239 patients with T-ALL enrolled at St. Jude and in the Italian national study AIEOP ALL-2000 were examined by gene expression profiling, flow cytometry and single nucleotide polymorphism array analysis. Probabilities of survival and treatment failure were calculated for subgroups considered to have ETP-ALL or typical T-ALL. Findings Thirty patients (12.6%) had leukemic lymphoblasts with an ETP-related gene expression signature or its associated distinctive immunophenotype (CD1a−, CD8−, CD5weak with stem-cell/myeloid markers). Cases of ETP-ALL showed increased genomic instability. Patients with this form of leukemia had a very high proportion of remission failure or hematologic relapse: 72% (95% confidence interval, 40% to 100%) at 10 years versus 10% (4% to 16%) for typical TALL patients treated at St. Jude; and 57% (25% to 89%) at 2 years versus 14% (6% to 22%) for patients treated in the AIEOP trial. Interpretation ETP-ALL is a distinct, previously unrecognized, pathobiologic entity that confers a dire prognosis with use of standard intensive chemotherapy. Its early recognition, using the criteria outlined here, is essential for the development of an effective clinical management strategy.
Subfields: Immunology, Pathology and Forensic Medicine, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/aa90b820f3344ddb4f7037f686e3607cd44852b0
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Citations in the corpus
- Biology, risk stratification, and therapy of pediatric acute leukemias: an update. (2011, background): “Early T-cell precursor ALL, a subset of T-cell ALL characterized by a gene expression profile similar to that of normal early thymic precursor cells with multilineage differentiation potential and a distinct immunophenotype (CD1a-negative, CD8-negative, CD5-weak, and the expression of stem-cell or m”
- The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. (2016, neutral): “D ow nloaded from http://ashpublications.org/blood/article-pdf/127/20/2391/1393154/2391.pdf by guest on 01 February 2022 early T-cell differentiation, with retention of some myeloid and stem cell characteristics at both the immunophenotypic and genetic level.128-131 By definition, blasts in ETP ALL ”
- THE GENOMIC LANDSCAPE OF PEDIATRIC AND YOUNG ADULT T-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA (2017, positive): “Prior studies have reported a mutational spectrum enriched for mutations in transcriptional, epigenetic and signaling genes more characteristic of myeloid malignancies 3,68 .”
- EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes (2012, background): “7) 3,560 (170-5,300) T-PLL (n=5) 5/5 90 (61-96) 214,000 (63,000-528,000) ATLL (n=4) 4/4 82 (39-85) 23,600 (3,200-34,900) CD4+ LGL (n=4) 4/4 25 (10-60) 2,300 (1,500-3,200) AITL (n=2) 2/2 5.”
- Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. (2015, background): “Early T-Cell Precursor ALL On the basis of gene expression profiling and flow cytometry, a collaborative study identified a distinct group of patients who represent approximately 12% of T-cell ALL with leukemia originating from a subset of thymocytes that retain a stem-cell–like feature.(38) Althoug”