Acute Lymphoblastic Leukemia

Harrison, Christine J.; Johansson, Bertil

doi:10.1002/9781118010136.ch9

Cited by 10 publications

(17 citation statements)

References 239 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings here, and those of others suggest that an unknown number of patients with hypotriploid or near triploid clones likely passed through a hyperhaploid stage without detection, and that the double chromosome number in a near triploid clone can become the dominating clone and mask the presence of a hyperhaploid origin. 5,11,36 In this study both routine cytogenetics and iFISH strategies were uninformative in identifying certain clones. Metaphase cytogenetics is known to be uninformative because of the low proliferation of the plasma cells, while iFISH can be uninformative because of improper probe selection or inappropriate cut-off values.…”

Section: Discussionmentioning

confidence: 88%

“…Accordingly, these clones appear to arise independently of hyperdiploid clones by a catastrophic loss of chromosomes from a diploid cell, as has been found in other hyperhaploid malignancies. 5,11 …”

Section: Discussionmentioning

confidence: 99%

“…5 We and others have previously reported a small number of hyperhaploid karyotypes in MM; 5-10 however, hyperhaploidy is most consistently identified and recognized as a category for numerical aberrations in childhood acute lymphoblastic leukemia (ALL). 11 In childhood ALL the hyperhaploid clones occur in two subgroups, a near-haploid group (25-29 chromosomes) and low hypodiploidy subgroup (30-39 chromosomes). 11 A distinctive set of five chromosomes occurs in hyperhaploid ALL with disomies of the X, Y, 14, 18, and 21.…”

Section: Introductionmentioning

confidence: 99%

“…11 In childhood ALL the hyperhaploid clones occur in two subgroups, a near-haploid group (25-29 chromosomes) and low hypodiploidy subgroup (30-39 chromosomes). 11 A distinctive set of five chromosomes occurs in hyperhaploid ALL with disomies of the X, Y, 14, 18, and 21. 11 In MM the hyperhaploid clone is characterized by a set of mostly odd numbered disomies including 3, 5, 7, 9, 11, 15, 18, 19, and 21.…”

Section: Introductionmentioning

confidence: 99%

“…11 A distinctive set of five chromosomes occurs in hyperhaploid ALL with disomies of the X, Y, 14, 18, and 21. 11 In MM the hyperhaploid clone is characterized by a set of mostly odd numbered disomies including 3, 5, 7, 9, 11, 15, 18, 19, and 21. Of note, in MM this is the same set of odd-numbered chromosomes found as trisomies in hyperdiploid myeloma, with the exception that chromosome 18 is retained in disomy in most of these cases.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma

et al. 2016

View full text Add to dashboard Cite

Hyperhaploid clones (24-34 chromosomes) were identified in 33 patients with multiple myeloma (MM), identifying a novel numerical cytogenetic subgroup. Strikingly, all hyperhaploid karyotypes were found to harbor monosomy 17p, the single most important risk stratification lesion in MM. A catastrophic loss of nearly a haploid set of chromosomes results in disomies of chromosomes 3, 5, 7, 9, 11, 15, 18, 19, and 21, the same basic set of odd-numbered chromosomes found in trisomy in hyperdiploid myeloma. All other autosomes are found in monosomy, resulting in additional clinically relevant monosomies of 1p, 6q, 13q, and 16q. Hypotriploid subclones (58-68 chromosomes) were also identified in 11 of the 33 patients and represent a duplication of the hyperhaploid clone. Analysis of clones utilizing interphase fluorescence in-situ hybridization (iFISH), metaphase FISH, and spectral karyotyping identified either monosomy 17 or del17p in all patients. Amplification of 1q21 was identified in eight patients, demonstrating an additional high-risk marker. Importantly, our findings indicate that current iFISH strategies may be uninformative or ambiguous in the detection of these clones, suggesting this patient subgroup maybe under-reported. Overall survival for patients with hyperhaploid clones was poor, with a five-year survival rate of 23.1%. These findings identify a distinct numerical subgroup with cytogenetically defined high-risk disease.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma

et al. 2016

View full text Add to dashboard Cite

show abstract

Optimizing the diagnostic workflow for acute lymphoblastic leukemia by optical genome mapping

et al. 2022

View full text Add to dashboard Cite

Acute lymphoblastic leukemia (ALL) is a malignancy that can be subdivided into distinct entities based on clinical, immunophenotypic and genomic features, including mutations, structural variants (SVs), and copy number alterations (CNA). Chromosome banding analysis (CBA) and Fluorescent In-Situ Hybridization (FISH) together with Multiple Ligation-dependent Probe Amplification (MLPA), array and PCR-based methods form the backbone of routine diagnostics. This approach is labor-intensive, time-consuming and costly. New molecular technologies now exist that can detect SVs and CNAs in one test. Here we apply one such technology, optical genome mapping (OGM), to the diagnostic work-up of 41 ALL cases. Compared to our standard testing pathway, OGM identified all recurrent CNAs and SVs as well as additional recurrent SVs and the resulting fusion genes. Based on the genomic profile obtained by OGM, 32 patients could be assigned to one of the major cytogenetic risk groups compared to 23 with the standard approach. The latter identified 24/34 recurrent chromosomal abnormalities, while OGM identified 33/34, misinterpreting only 1 case with low hypodiploidy. The results of MLPA were concordant in 100% of cases.Overall, there was excellent concordance between the results. OGM increased the detection rate and cytogenetic resolution, and abrogated the need for cascade testing, resulting in reduced turnaround times. OGM also provided opportunities for better patient stratification and accurate treatment options. However, for comprehensive cytogenomic testing, OGM still needs to be complemented with CBA or SNP-array to detect ploidy changes and with BCR::ABL1 FISH to assign patients as soon as possible to targeted therapy.Katrina Rack and Jolien De Bie are co-first authors. Lucienne Michaux and Barbara Dewaele are co-senior authors.

show abstract

The role of the RAS pathway in iAMP21-ALL

et al. 2016

View full text Add to dashboard Cite

Intrachromosomal amplification of chromosome 21 (iAMP21) identifies a high-risk subtype of acute lymphoblastic leukaemia (ALL), requiring intensive treatment to reduce their relapse risk. Improved understanding of the genomic landscape of iAMP21-ALL will ascertain whether these patients may benefit from targeted therapy. We performed whole-exome sequencing of eight iAMP21-ALL samples. The mutation rate was dramatically disparate between cases (average 24.9, range 5-51) and a large number of novel variants were identified, including frequent mutation of the RAS/MEK/ERK pathway. Targeted sequencing of a larger cohort revealed that 60% (25/42) of diagnostic iAMP21-ALL samples harboured 42 distinct RAS pathway mutations. High sequencing coverage demonstrated heterogeneity in the form of multiple RAS pathway mutations within the same sample and diverse variant allele frequencies (VAF) (2-52%), similar to other subtypes of ALL. Constitutive RAS pathway activation was observed in iAMP21 samples that harboured mutations in the predominant clone (≥35% VAF). Viable iAMP21 cells from primary xenografts showed reduced viability in response to the MEK1/2 inhibitor, selumetinib, in vitro. As clonal (≥35% VAF) mutations were detected in 26% (11/42) of iAMP21-ALL, this evidence of response to RAS pathway inhibitors may offer the possibility to introduce targeted therapy to improve therapeutic efficacy in these high-risk patients.

show abstract

Acute Lymphoblastic Leukemia

Cited by 10 publications

References 239 publications

Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma

Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma

Optimizing the diagnostic workflow for acute lymphoblastic leukemia by optical genome mapping

The role of the RAS pathway in iAMP21-ALL

Contact Info

Product

Resources

About