Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial

Moorman, Anthony V.; Ensor, Hannah; Richards, Sue; Chilton, Lucy; Schwab, Claire; Kinsey, Sally; Vora, Ajay; Mitchell, Chris; Harrison, Christine J.

doi:10.1016/s1470-2045(10)70066-8

Cited by 354 publications

(377 citation statements)

References 37 publications

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“…The translocation is cryptic in the vast majority of cases, being undetectable by conventional karyotyping [7]. The resultant ETV6-RUNX1 (previously called the TEL-AML1) fusion protein converts RUNX1 from a transcriptional activator to a repressor.…”

Section: Dear Readersmentioning

confidence: 99%

“…Clinically, ETV6-RUNX1 is a good prognostic factor, found in children aged 1-10 years, with CD10 ? ALL and characterized by late relapses with excellent chemosensitivity [2,7]. From a laboratory perspective, as the Aydin paper [1] illustrates, FISH probes for the ETV6/RUNX1 fusion also enable presumptive identification of aneuploidies of chromosomes 12 or 21 as well as ETV6or RUNX1 deletions or amplifications.…”

Section: Dear Readersmentioning

confidence: 99%

“…From a laboratory perspective, as the Aydin paper [1] illustrates, FISH probes for the ETV6/RUNX1 fusion also enable presumptive identification of aneuploidies of chromosomes 12 or 21 as well as ETV6or RUNX1 deletions or amplifications. The poor prognostic intra-chromosomal amplification of chromosome 21 (iAMP21) is also detectable by this modality [7,8].…”

Section: Dear Readersmentioning

confidence: 99%

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Old and New Prognostic Markers in Pediatric ALL

Pati¹,

Sharma²

2016

Indian J Hematol Blood Transfus

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Section: Dear Readersmentioning

confidence: 99%

Section: Dear Readersmentioning

confidence: 99%

Section: Dear Readersmentioning

confidence: 99%

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Old and New Prognostic Markers in Pediatric ALL

Pati¹,

Sharma²

2016

Indian J Hematol Blood Transfus

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“…With the use of modern intensive therapy, pediatric ALL patients with t(1;19) have an intermediate/good response [14]. In adults with t(1;19), the prognosis remains controversial, with some studies reporting poor outcomes while others found to association with outcome.…”

Section: A) Primary Chromosomal Abnormalities (I) Chromosomal Translomentioning

confidence: 99%

Routine Cytogenetic Analysis of Chromosome Abnormalities in Acute Lymphoblastic Leukemia

Meng¹

2015

Int Jour of Biomed Res

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Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Acquired chromosomal and genetic abnormalities have been used to define distinct biological and clinical subtypes of ALL. These aberrations have been shown to be associated with patient outcome and are used to direct therapy. Conventional cytogenetics analysis (CCA) is currently the gold standard to detect chromosome abnormalities in hematological malignancies. In this review we briefly describe the CCA methodology, advantages and limitations of CCA, the main chromosomal abnormalities and their prognostic significance in ALL.

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“…This underlies the need for new therapeutic options for resistant patients. The role of recurrent chromosomal translocations in the pathogenesis of ALL has been clearly established 2 providing not only important prognostic information but also guiding the development of new treatments such as the use of tyrosinekinase inhibitors (imatinib or dasatinib) in patients with t(9;22). 3 Other genetic alterations such as the overexpression of FLT3 receptor tyrosine kinase in mixed-lineage leukemia gene-rearranged or hyperdiploid B-ALL 4 or the presence of NOTCH1-activating mutations in T-cell ALL are attractive candidates for targeted therapies with FLT3 or NOTCH inhibitors (g-secretase inhibitors).…”

Section: Introductionmentioning

confidence: 99%

Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia

et al. 2012

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Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I --II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/ c-RAG2 À/À gc À/À mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2 À/À gc À/À mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL.

show abstract

Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial

Cited by 354 publications

References 37 publications

Old and New Prognostic Markers in Pediatric ALL

Old and New Prognostic Markers in Pediatric ALL

Routine Cytogenetic Analysis of Chromosome Abnormalities in Acute Lymphoblastic Leukemia

Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia

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