Analysis of a breakpoint cluster reveals insight into the mechanism of intrachromosomal amplification in a lymphoid malignancy.

@article{Sinclair2011AnalysisOA,
  title={Analysis of a breakpoint cluster reveals insight into the mechanism of intrachromosomal amplification in a lymphoid malignancy.},
  author={Paul B. Sinclair and Helen Parker and Qian An and Vikki Rand and Hannah Ensor and Christine J Harrison and Jonathan C. Strefford},
  journal={Human molecular genetics},
  year={2011},
  volume={20 13},
  pages={
          2591-602
        }
}
A distinct sub-group of B-cell precursor acute lymphoblastic leukemia, defined by intrachromosomal amplification of chromosome 21 (iAMP21), is restricted to older children and has been associated with a poor outcome. Accurate diagnosis is important for appropriate risk stratification for treatment. It could be improved by understanding the initiating mechanism. iAMP21 is characterized by amplification of a 5.1-24 Mb region of chromosome 21, which includes the RUNX1 gene. It is thought to arise… 
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An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome
TLDR
These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given, reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP 21 patients.
Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report
TLDR
The clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described.
Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia
TLDR
It is shown that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population.
Cytogenetic Variation of B-Lymphoblastic Leukemia With Intrachromosomal Amplification of Chromosome 21 (iAMP21): A Multi-Institutional Series Review.
TLDR
The findings not only demonstrate that B-ALL with iAMP21 is truly a distinct clinicopathologic entity but also suggest that a subset of cases of B-all with iamp21 can show variable cytogenetic features.
Integration of cytogenomic data for furthering the characterization of pediatric B-cell acute lymphoblastic leukemia: a multi-institution, multi-platform microarray study.
Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia
TLDR
This is the first study to show significant correlation with iAMP21-positive ALL, the cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia.
Coexistence of iAMP21 and ETV6-RUNX1 fusion in an adolescent with B cell acute lymphoblastic leukemia: literature review of six additional cases
TLDR
High-resolution single nucleotide polymorphism microarray (SNP array) revealed the iAMP21 to be chromothripsis of 21q and subsequent metaphase FISH further delineated complex genomic aberrations.
Mechanisms and clinical applications of chromosomal instability in lymphoid malignancy
TLDR
The means by which chromosome‐level genetic aberrations may give rise to multiple pathogenic mutations required for carcinogenesis are discussed and a discussion of the clinical applications of CIN and aneuploidy to diagnosis, prognosis and therapy is discussed.
MLPA as a complementary tool for diagnosis of chromosome 21 aberrations in childhood BCP-ALL
Chromosome 21 abnormalities are the most frequent genetic findings in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL) cases. Majority of patients are effectively diagnosed with…
Genomic profiling of B-progenitor acute lymphoblastic leukemia.
  • C. Mullighan
  • Biology
    Best practice & research. Clinical haematology
  • 2011
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