Compendium of Cancer Genome Aberrations

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HAEM5:B-lymphoblastic leukaemia/lymphoma with iAMP21 (view source)

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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
 
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
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{{Under Construction}}
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<br />
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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-04. The original page can be found at [[HAEM4:B-Lymphoblastic Leukemia/Lymphoma with iAMP21]].
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}}</blockquote>
   
==Primary Author(s)*==
 
==Primary Author(s)*==
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Holli M. Drendel, PhD, FACMGG, Carolinas Pathology Group, Charlotte  
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Holli M. Drendel, PhD, FACMGG, Carolinas Pathology Group, Charlotte
    
__TOC__
 
__TOC__
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==Cancer Category / Type==
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==Cancer Category/Type==
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B-lymphoblastic leukemia/lymphoma
 
B-lymphoblastic leukemia/lymphoma
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==Definition / Description of Disease==
 
==Definition / Description of Disease==
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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=":0">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>
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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==
 
==Synonyms / Terminology==
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Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
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Put your text here
    
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
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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=":1">{{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=05 2020|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>
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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>
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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=":1" />
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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==
 
==Clinical Features==
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Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
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~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"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
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|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
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|N/A
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EXAMPLE B-symptoms (weight loss, fever, night sweats)
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EXAMPLE Fatigue
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EXAMPLE Lymphadenopathy (uncommon)
   
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|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
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|EXAMPLE Cytopenias
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|Low platelet count
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Low WBC count (<50,000/μl)
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EXAMPLE Lymphocytosis (low level)
   
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|}
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
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Patients tend to present with a low platelet count and low WBC count (<50,000/µl). ~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>
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</blockquote>
   
==Sites of Involvement==
 
==Sites of Involvement==
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==Morphologic Features==
 
==Morphologic Features==
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There are no unique morphological or cytochemical features that distinguish this entity from other types of ALL.<ref name=":0" />
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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>{{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>
 
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>
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[[File:IAMP21 met.jpg|thumb|515x515px|iAMP21 in a ring formation; Courtesy of Fullerton Genetics Lab|alt=|center]]
   
<br />
 
<br />
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[[File:IAMP21 met.jpg|center|thumb|875x875px|iAMP21 in a ring formation; Courtesy of Fullerton Genetics Lab]]
    
==Immunophenotype==
 
==Immunophenotype==
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No detailed information is known, other than these cases occur exclusively in B-ALL.<ref name=":0" />
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No detailed information is known, other than these cases occur exclusively in B-ALL.<ref name=":02" />
    
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Finding!!Marker
 
!Finding!!Marker
 
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|-
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|Positive (universal)||EXAMPLE CD1
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|Positive (universal)||N/A
 
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|-
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|Positive (subset)||EXAMPLE CD2
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|Positive (subset)||N/A
 
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|-
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|Negative (universal)||EXAMPLE CD3
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|Negative (universal)||N/A
 
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|-
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|Negative (subset)||EXAMPLE CD4
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|Negative (subset)||N/A
 
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|}
    
==Chromosomal Rearrangements (Gene Fusions)==
 
==Chromosomal Rearrangements (Gene Fusions)==
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Put your text here and fill in the table
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Some rearrangements have been seen as secondary abnormalities.
    
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!Therapeutic Significance (Yes, No or Unknown)
 
!Therapeutic Significance (Yes, No or Unknown)
 
!Notes
 
!Notes
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|-
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|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
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EXAMPLE 30% (add reference)
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|Yes
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|No
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|EXAMPLE
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The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
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<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
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Some rearrangements have been seen as secondary abnormalities.
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{| class="wikitable sortable"
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!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
   
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|del(X)(p22.33p22.33)/del(Y)(p11.32p11.32)||''P2RY8-CRLF2''||der(X)/der(Y)||
 
|del(X)(p22.33p22.33)/del(Y)(p11.32p11.32)||''P2RY8-CRLF2''||der(X)/der(Y)||
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|Because of the unique nature of the iAMP21 abnormality, cases that present with additional genomic lesions that may suggest another category, such as a CRLF2 rearrangement, should still be classified as B-ALL with iAMP21.
 
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|-
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|t(12;21)(p13.2;q22.1)||''ETV6-RUNX1''||der(21)||
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|t(12;21)(p13.2;q22.1)
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|''ETV6-RUNX1''
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|der(21)
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|t(9;22)(q34;q11.2)
 
|t(9;22)(q34;q11.2)
 
|''BCR-ABL1''
 
|''BCR-ABL1''
 
|der(22)
 
|der(22)
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</blockquote>
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==Individual Region Genomic Gain/Loss/LOH==
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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.
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
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* Chromosomal Rearrangements (Gene Fusions)
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* Individual Region Genomic Gain/Loss/LOH
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* Characteristic Chromosomal Patterns
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* Gene Mutations (SNV/INDEL)}}
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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.  
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Because of the unique nature of the iAMP21 abnormality, cases that present with additional genomic lesions that may suggest another category, such as a CRLF2 rearrangement, should still be classified as B-ALL with iAMP21.
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</blockquote>
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==Individual Region Genomic Gain / Loss / LOH==
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
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|EXAMPLE
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|X
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|EXAMPLE Loss
   
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Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
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|EXAMPLE
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|EXAMPLE Gain
   
|EXAMPLE
 
|EXAMPLE
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Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
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<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
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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.
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{| class="wikitable sortable"
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!Chromosome Number!!Gain/Loss/Amp/LOH
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|X
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|Gain
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|10
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|Gain
   
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|14
 
|14
 
|Gain
 
|Gain
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|7/7q
 
|7/7q
 
|Loss
 
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|11q
 
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|Loss
 
|Loss
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</blockquote>
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==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
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Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
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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" /><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>
    
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
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|EXAMPLE
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|Amplification of RUNX1
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|
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Co-deletion of 1p and 18q
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|
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|Yes
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|
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|No
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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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|No
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|-
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|EXAMPLE:
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|Terminal deletion of 21q
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|
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See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
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|
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[[File:IAMP21 CMA .png|center|thumb|1028x1028px|Characteristic iAMP21 CMA; Courtesy of Fullerton Genetics Lab]]
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<br />
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==Gene Mutations (SNV/INDEL)==
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<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
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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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[[File:IAMP21 CMA .png|center|thumb|861x861px|Characteristic iAMP21 CMA; Courtesy of Fullerton Genetics Lab]]
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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. Further, it often is accompanied by a terminal deletion of 21q. 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>
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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. This is part of the critical region consistently amplified (chr21:32.8-37.9 Mb, GRCh37/hg19). 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=":1" /><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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</blockquote>
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==Gene Mutations (SNV / INDEL)==
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
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|EXAMPLE: TP53; Variable LOF mutations
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|NRAS
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EXAMPLE:
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EGFR; Exon 20 mutations
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EXAMPLE: BRAF; Activating mutations
   
|EXAMPLE: TSG
 
|EXAMPLE: TSG
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|EXAMPLE: 20% (COSMIC)
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|45%
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  −
EXAMPLE: 30% (add Reference)
   
|EXAMPLE: IDH1 R123H
 
|EXAMPLE: IDH1 R123H
 
|EXAMPLE: EGFR amplification
 
|EXAMPLE: EGFR amplification
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|
 
|
 
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
 
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
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<br />
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|}
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Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
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<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
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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=":1" /><ref name=":2" /> 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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{| class="wikitable sortable"
   
|-
 
|-
−
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
+
|KRAS
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|-
+
|
−
|''NRAS''|| || || ||45%
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|18%
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|-
+
|
−
|''KRAS''
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|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
−
|18%
   
|-
 
|-
 
|''FLT3''
 
|''FLT3''
 +
|
 +
|20%
 +
|
 +
|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
−
|20%
   
|-
 
|-
 
|''PTPN11''
 
|''PTPN11''
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|
 +
|11%
 +
|
 +
|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
−
|11%
   
|-
 
|-
 
|''BRAF''
 
|''BRAF''
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|
 +
|2%
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|
 +
|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
−
|2%
   
|-
 
|-
 
|''NF1''
 
|''NF1''
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|
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|2%
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|
 +
|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
−
|2%
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|}
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===Other Mutations===
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{| class="wikitable sortable"
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|-
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!Type!!Gene/Region/Other
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|-
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|Concomitant Mutations||EXAMPLE IDH1 R123H
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|-
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|Secondary Mutations||EXAMPLE Trisomy 7
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|-
  −
|Mutually Exclusive||EXAMPLE EGFR Amplification
   
|}
 
|}
 +
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
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</blockquote>
   
==Epigenomic Alterations==
 
==Epigenomic Alterations==
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Put your text here
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N/A
    
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
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Put your text here and fill in the table
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|RUNX1
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|EXAMPLE: MAPK signaling
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|RAS pathway<ref name=":2" />
 
|EXAMPLE: Increased cell growth and proliferation
 
|EXAMPLE: Increased cell growth and proliferation
 
|-
 
|-
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|EXAMPLE:  Abnormal gene expression program
 
|EXAMPLE:  Abnormal gene expression program
 
|}
 
|}
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<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
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''[[RUNX1]]''
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RAS pathway<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>
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</blockquote>
   
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
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Different methodologies are able to detect the iAMP21, such as:
 
Different methodologies are able to detect the iAMP21, such as:
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==Familial Forms==
 
==Familial Forms==
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Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
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N/A
    
==Additional Information==
 
==Additional Information==
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Put your text here
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N/A
    
==Links==
 
==Links==
    
[[RUNX1]]
 
[[RUNX1]]
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Put your links here (use "Link" icon at top of page)
      
==References==
 
==References==
 
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
 
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
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'''
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<br />
    
==Notes==
 
==Notes==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with iAMP21”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_iAMP21</nowiki>.
 
<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with iAMP21”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_iAMP21</nowiki>.
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[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases B]]
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[[Category:HAEM5]]
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[[Category:DISEASE]]
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[[Category:Diseases B]]
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