HAEM5:B-lymphoblastic leukaemia/lymphoma with iAMP21: Difference between revisions

==Gene Rearrangements==

Some rearrangements have been seen as secondary abnormalities.

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|t(12;21)(p13.2;q22.1)

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==Characteristic Chromosomal or Other Global Mutational Patterns==

iAMP21 cases have a characteristic pattern that is both complex and variable. This pattern comprises multiple regions of gain, amplification and deletion. Interestingly, ''RUNX1'' amplification is not always intrachromosomal.<ref>{{Cite journal|last=Arber|first=Daniel A.|date=04 2019|title=The 2016 WHO classification of acute myeloid leukemia: What the practicing clinician needs to know|url=https://pubmed.ncbi.nlm.nih.gov/30926096|journal=Seminars in Hematology|volume=56|issue=2|pages=90–95|doi=10.1053/j.seminhematol.2018.08.002|issn=1532-8686|pmid=30926096}}</ref><ref>{{Cite journal|last=Johnson|first=Ryan C.|last2=Weinberg|first2=Olga K.|last3=Cascio|first3=Michael J.|last4=Dahl|first4=Gary V.|last5=Mitton|first5=Bryan A.|last6=Silverman|first6=Lewis B.|last7=Cherry|first7=Athena M.|last8=Arber|first8=Daniel A.|last9=Ohgami|first9=Robert S.|date=2015-07|title=Cytogenetic Variation of B-Lymphoblastic Leukemia With Intrachromosomal Amplification of Chromosome 21 (iAMP21): A Multi-Institutional Series Review|url=https://pubmed.ncbi.nlm.nih.gov/26071468|journal=American Journal of Clinical Pathology|volume=144|issue=1|pages=103–112|doi=10.1309/AJCPLUYF11HQBYRB|issn=1943-7722|pmid=26071468}}</ref> The formation of iAMP21 is considered to be due to breakage-fusion-bridge cycles followed by chromothripsis and other complex structural rearrangements of chromosome 21. Studies, molecular and cytogenetic, have elucidated a common 5.1 Mb region that includes the ''RUNX1'' gene. However, even though ''RUNX1'' is included in the amplified region, there has not yet been any conclusive evidence that ''RUNX1'' is critical in the pathogenesis of disease given that it is not overexpressed in some individuals with this abnormality.<ref name=":0">{{Cite journal|last=Akkari|first=Yassmine M. N.|last2=Bruyere|first2=Helene|last3=Hagelstrom|first3=R. Tanner|last4=Kanagal-Shamanna|first4=Rashmi|last5=Liu|first5=Jie|last6=Luo|first6=Minjie|last7=Mikhail|first7=Fady M.|last8=Pitel|first8=Beth A.|last9=Raca|first9=Gordana|date=2020-05|title=Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32302940|journal=Cancer Genetics|volume=243|pages=52–72|doi=10.1016/j.cancergen.2020.03.001|issn=2210-7762|pmid=32302940}}</ref><ref>{{Cite journal|last=Rand|first=Vikki|last2=Parker|first2=Helen|last3=Russell|first3=Lisa J.|last4=Schwab|first4=Claire|last5=Ensor|first5=Hannah|last6=Irving|first6=Julie|last7=Jones|first7=Lisa|last8=Masic|first8=Dino|last9=Minto|first9=Lynne|date=2011-06-23|title=Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21527530|journal=Blood|volume=117|issue=25|pages=6848–6855|doi=10.1182/blood-2011-01-329961|issn=1528-0020|pmid=21527530}}</ref><ref>{{Cite journal|last=Hunger|first=Stephen P.|last2=Lu|first2=Xiaomin|last3=Devidas|first3=Meenakshi|last4=Camitta|first4=Bruce M.|last5=Gaynon|first5=Paul S.|last6=Winick|first6=Naomi J.|last7=Reaman|first7=Gregory H.|last8=Carroll|first8=William L.|date=2012-05-10|title=Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group|url=https://pubmed.ncbi.nlm.nih.gov/22412151|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=30|issue=14|pages=1663–1669|doi=10.1200/JCO.2011.37.8018|issn=1527-7755|pmc=3383113|pmid=22412151}}</ref>

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!Chromosomal Pattern

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|See CMA image displaying the amplification of RUNX1. This is part of the critical region consistently amplified: chr21:32.8-37.9 Mb (hg19).

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In a 2016 paper, it was shown that in the iAMP21-ALL exome, the mutations were more commonly transitions (for example: C>T) than transversions or indels.<ref name=":0" /><ref name=":2">{{Cite journal|last=Ryan|first=S. L.|last2=Matheson|first2=E.|last3=Grossmann|first3=V.|last4=Sinclair|first4=P.|last5=Bashton|first5=M.|last6=Schwab|first6=C.|last7=Towers|first7=W.|last8=Partington|first8=M.|last9=Elliott|first9=A.|date=09 2016|title=The role of the RAS pathway in iAMP21-ALL|url=https://pubmed.ncbi.nlm.nih.gov/27168466|journal=Leukemia|volume=30|issue=9|pages=1824–1831|doi=10.1038/leu.2016.80|issn=1476-5551|pmc=5017527|pmid=27168466}}</ref> Frequently, mutations in the RAS signaling pathway have been observed. Interestingly, these mutations were observed to coexist in patterns ranging from 2-3 mutated genes to 2-4 mutations in the same gene in one sample. Further, the ''FLT3''-ITD was more prevalent in iAMP21-ALL.<ref name=":2" />

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==Epigenomic Alterations==

|RAS pathway<ref name=":2" />

|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation

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==Genetic Diagnostic Testing Methods==