HAEM5:B-lymphoblastic leukaemia/lymphoma with iAMP21: Difference between revisions
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{{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with iAMP21}} | {{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with iAMP21}} | ||
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] | ||
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< | ==Definition / Description of Disease== | ||
Intrachromosomal amplification of chromosome 21 (iAMP21) is a neoplasm of lymphoblasts that are of the B-cell lineage. It is characterized by amplification of the ''RUNX1'' gene at 21q22.3 on a structurally abnormal chromosome 21. Amplification is defined as ≥5 copies of ''RUNX1'' detected by FISH or ≥3 copies of ''RUNX1'' on a single abnormal chromosome 21.<ref name=":02">Borowitz MJ, et al., (2017). B-Lymphoblastic leukaemia/lymphoma with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France.</ref> | |||
==Synonyms / Terminology== | |||
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==Epidemiology / Prevalence== | |||
iAMP21 is observed most often in the older pediatric group (median age of 9 years, with a range of 2-30 years). It accounts for ~2% of B-ALL cases including ~2% of standard-risk and 3% of high-risk patients. The incidence in adult B-ALL has not been established; however, it appears to be less prevalent than in the pediatric population.<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> | |||
Further, patients carrying a rob(15;21)(q10;q10) have an ~2700-fold increased risk of developing iAMP21 ALL compared to the general population. Additionally, patients with a constitutional ring chromosome 21, r(21), may potentially be predisposed to iAMP21 ALL.<ref name=":0" /> | |||
==Clinical Features== | |||
~50% of cases are classified as high-risk based on an age of ≥10 years.<ref>{{Cite journal|last=Harrison|first=Christine J.|date=2015-02-26|title=Blood Spotlight on iAMP21 acute lymphoblastic leukemia (ALL), a high-risk pediatric disease|url=https://pubmed.ncbi.nlm.nih.gov/25608562|journal=Blood|volume=125|issue=9|pages=1383–1386|doi=10.1182/blood-2014-08-569228|issn=1528-0020|pmid=25608562}}</ref> Pediatric iAMP21 has been associated with a poor outcome. It displays an increased rate of relapse when treated on standard protocols. Further, the event-free survival and overall survival were significantly worse for individuals with the iAMP21 and standard-risk B-ALL, but not significant in individuals with iAMP21 and high-risk B-ALL. | |||
{| class="wikitable" | |||
|'''Signs and Symptoms''' | |||
|N/A | |||
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|'''Laboratory Findings''' | |||
|Low platelet count | |||
Low WBC count (<50,000/μl) | |||
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==Sites of Involvement== | |||
Bone Marrow and peripheral blood | |||
==Morphologic Features== | ==Morphologic Features== | ||
There are no unique morphological or cytochemical features that distinguish this entity from other types of ALL.<ref name=":02" | There are no unique morphological or cytochemical features that distinguish this entity from other types of ALL.<ref name=":02" /> | ||
Cytogenetic morphology of the abnormal chromosome 21 can vary markedly between patients.<ref | Cytogenetic morphology of the abnormal chromosome 21 can vary markedly between patients.<ref>{{Cite journal|last=Harewood|first=L.|last2=Robinson|first2=H.|last3=Harris|first3=R.|last4=Al-Obaidi|first4=M. Jabbar|last5=Jalali|first5=G. R.|last6=Martineau|first6=M.|last7=Moorman|first7=A. V.|last8=Sumption|first8=N.|last9=Richards|first9=S.|date=2003-03|title=Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases|url=https://pubmed.ncbi.nlm.nih.gov/12646943|journal=Leukemia|volume=17|issue=3|pages=547–553|doi=10.1038/sj.leu.2402849|issn=0887-6924|pmid=12646943}}</ref> | ||
<br /> | <br /> | ||
[[File:IAMP21 met.jpg|center|thumb|875x875px|iAMP21 in a ring formation; Courtesy of Fullerton Genetics Lab]] | |||
==Immunophenotype== | ==Immunophenotype== | ||
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In ~80% of iAMP21 B-ALL cases, recurrent secondary abnormalities, both chromosomal and molecular, have been documented. Deletions involving particular genes such as; ''IKZF1, CDKN2A/B, PAX5, SH2B3, ETV6'' and ''RB1'' have also been observed. | In ~80% of iAMP21 B-ALL cases, recurrent secondary abnormalities, both chromosomal and molecular, have been documented. Deletions involving particular genes such as; ''IKZF1, CDKN2A/B, PAX5, SH2B3, ETV6'' and ''RB1'' have also been observed. | ||
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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" | 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" /><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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==Additional Information== | ==Additional Information== | ||
N/A | |||
==Links== | ==Links== | ||