Acute lymphoblastic leukemia

Harrison, Christine J.; Johansson, Bertil

doi:10.1002/9781118795569.ch10

Cited by 10 publications

(6 citation statements)

References 304 publications

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“…This includes rob (15;21), an important predisposing factor to ALL with iAMP21. 27,28 Interestingly, the OGM software failed to detect a t(X;14), an abnormality associated with intermediate to poor prognosis, 11,[29][30][31][32][33][34] although it was clearly visible during manual inspection. The nondetection of abnormalities involving the PAR1 region has previously been reported.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…1). 5 Trial‐based studies showed that these cytogenetic subgroups correlated with age and were strongly linked to outcome 6 . For example, the translocation, t(12;21)(p13;q22)/ ETV6‐RUNX1 fusion, and high hyperdiploidy (51–65 chromosomes) occur predominantly in children, together they account for more than 50% of childhood BCP‐ALL, and are associated with a good prognosis.…”

Section: Cytogenetics Of Bcp‐all: a Historical Perspectivementioning

confidence: 99%

“…1). 5 Trial-based studies showed Funding/support: Bloodwise, UK. Disclosure: The authors have indicated they have no potential conflicts of interest to disclose.…”

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confidence: 99%

Advances in B‐cell Precursor Acute Lymphoblastic Leukemia Genomics

Schwab

Harrison

2018

HemaSphere

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In childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), cytogenetic abnormalities remain important diagnostic and prognostic tools. A number of well-established abnormalities are routinely used in risk stratification for treatment. These include high hyperdiploidy and ETV6-RUNX1 fusion, classified as good risk, while Philadelphia chromosome (Ph) positive ALL and rearrangements of the KMT2A (MLL) gene define poor risk. A poor risk subgroup of intrachromosomal amplification of chromosome 21 (iAMP21-ALL) has been described, in which intensification of therapy has greatly improved outcome.Until recently, no consistent molecular features were defined in around 30% of BCP-ALL (known as B-other-ALL). Recent studies are classifying them into distinct subgroups, some with clear potential for novel therapeutic approaches. For example, in 1 poor risk subtype, known as Ph-like/BCR-ABL1-like ALL, approximately 10% have rearrangements of ABL-class tyrosine kinases: including ABL1, ABL2, PDGFRB, PDGFRA, and CSF1R. Notably, they show a poor response to standard chemotherapy, while they respond to treatment with tyrosine kinase inhibitors, such as imatinib. In other Ph-like-ALL patients, deregulation of the cytokine receptor, CRLF2, and JAK2 rearrangements lead to activation of the JAK-STAT signaling pathway, implicating a specific role for JAK inhibitors in their treatment. Other novel subgroups within B-other-ALL are defined by the IGH-DUX4 translocation, related to deletions of the ERG gene and a good outcome, while fusions involving ZNF384, MEF2D, and intragenic PAX5 amplification (PAX5AMP) are linked to a poor outcome. Continued genetic screening will eventually lead to complete genomic classification of BCP-ALL and define more molecular targets for less toxic therapies.

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“…Leukemia is one of the important causes of mortality in both developed and developing countries; as a result, it burdens high expenses to health scope (5). It has been predicted that deaths of about 50% younger patients and 90% older patients are because of acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL), respectively (6,7).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Effects on Seeds of Cancer Survival in Leukemia

2021

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The cancer metabolic alteration is considered a hallmark and fast becoming a road for therapeutic intervention. Mitochondria have been regarded as essential cell elements that fuel the metabolic needs of most cancer cell types. Leukemia stem cells (LSCs) are a heterogeneous, highly self-renewing, and pluripotent cell population within leukemic cells. The most important source of ATP and metabolites to fulfill the bioenergetics and biosynthetic needs of most cancer stem cells is the mitochondria. In addition, mitochondria have a core role in autophagy and cell death and are the main source of reactive oxygen species (ROS) generation. Overall, growing evidence now shows that mitochondrial activities and pathways have changed to adapt with different types of leukemia, thus mitochondrial metabolism could be targeted for blood malignancy therapy. This review focuses on the function of mitochondria in LSC of the different leukemia types.

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Acute lymphoblastic leukemia

Cited by 10 publications

References 304 publications

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

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

Advances in B‐cell Precursor Acute Lymphoblastic Leukemia Genomics

Mitochondrial Effects on Seeds of Cancer Survival in Leukemia

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