Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia

Coustan‐Smith, Elaine; Mullighan, Charles G.; Onciu, Mihaela; Behm, Frederick G.; Raimondi, Susana C.; Pei, Deqing; Cheng, Cheng; Su, Xiaoping; Rubnitz, Jeffrey E.; Basso, Giuseppe; Biondi, Andrea; Pui, Ching Hon; Downing, James R.; Campana, Dario

doi:10.1016/s1470-2045(08)70314-0

Cited by 866 publications

(1,041 citation statements)

References 40 publications

Supporting

Mentioning

968

Contrasting

Unclassified

Order By: Relevance

“…The definition of the ETP immunophenotype was as described by Coustan-Smith et al [35]: absent (<5%) CD1a and CD8, weak (<75%) CD5, and an expression of 25% or more of one or more of the following: CD117, CD34, HLA-DR, CD13, CD33, CD11b, or CD65.…”

Section: Immunophenotypesmentioning

confidence: 99%

“…The threshold for homozygous deletions by Q-PCR was defined as a fold-change <0. 35 advances in the molecular typing of leukemia, many new genetic alterations, including mutations and deletions, have been identified. However, their prognostic values have not been widely verified and the results may be controversial [24][25][26][27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

“…Two independent studies identified pediatric patients with T-cell ALL that had very poor initial treatment responses and clinical outcomes [35,36]. Coustan-Smith et al [35] found that patients with early T-cell precursor leukemia (ETP-ALL), accounting for around 12% of pediatric T-cell ALL, had very high incidences of treatment failure.…”

Section: Introductionmentioning

confidence: 99%

“…Coustan-Smith et al [35] found that patients with early T-cell precursor leukemia (ETP-ALL), accounting for around 12% of pediatric T-cell ALL, had very high incidences of treatment failure. The prognostic value of ETP-ALL was even more significant than minimal residual disease.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Yang

Hsiao

Chen

et al. 2011

Pediatric Blood & Cancer

View full text Add to dashboard Cite

BackgroundThe absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T‐cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T‐cell ALL.ProcedureForty‐five children with T‐cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q‐PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q‐PCR was defined as a fold‐change <0.35.ResultsABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23–53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10–16.42).ConclusionsThe absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T‐cell ALL in Taiwan. Providing patients with T‐cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials. Pediatr Blood Cancer 2012; 58: 846–851. © 2011 Wiley Periodicals, Inc.

show abstract

Section: Immunophenotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Yang

Hsiao

Chen

et al. 2011

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

“…Deregulated tyrosine kinase signaling was detected in human T cell acute lymphoblastic leukemia, but activating KIT mutations were not reported [41]. KIT is frequently expressed in early T cell precursor ALL, but this expression may reflect the immature cell origin rather than being linked to malignant transformation [42]. Kit D814V transgenic mice rarely developed a T cell ALL-like disease which may stem either from uncommitted lymphoid progenitors or from cells that were already committed to T cell development.…”

Section: Discussionmentioning

confidence: 99%

Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in mice

Weidemann

Behrendt

Schoedel

et al. 2017

Experimental Hematology

View full text Add to dashboard Cite

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and is of pro-or pre-B cell origin in most cases. The receptor tyrosine kinase KIT is expressed by hematopoietic stem and precursor cells. Gain-of-function mutations of KIT cause systemic mastocytosis, which is characterized by abnormal accumulations of mast cells. We previously reported a mouse model of mastocytosis based on conditional expression of a constitutively active Kit protein. Half of these animals developed leukemic disease of B lineage origin. Herein, we report that this condition bears striking similarities to human B-ALL. The immuno-phenotype of the leukemic cells was compatible with a pro-B cell origin, as was the finding of immunoglobulin heavy chain gene rearrangements in all cases, whereas light chain loci were mostly not rearranged. Leukemogenesis was independent of pre-B cell receptor expression.Primary leukemic cells and permanent cell lines derived from these were serially transplantable and rapidly killed the recipients. In few animals, the leukemia was of T cell origin with abnormal CD4/8 double positive T cell precursors dominating in the circulation. In summary, we report a novel ALL mouse model that may prove useful for in vivo drug testing and identification of novel oncogenic mutations and principles.

show abstract

Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia

2018

Self Cite

View full text Add to dashboard Cite

Therapies targeting specific transcripts or leukemic cell surface antigens are major breakthroughs in the treatment of adults with ALL. The incorporation of new monoclonal antibodies and other targeted approaches into frontline regimens is showing promising results. If confirmed, such strategies may increase the cure rates in adults to levels achieved in pediatric ALL and reduce the need for intensive and prolonged chemotherapy.

show abstract

Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia

Cited by 866 publications

References 40 publications

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in mice

Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About