Compendium of Cancer Genome Aberrations

HAEM5:B lymphoblastic leukaemia/lymphoma with IGH::IL3 fusion: Difference between revisions

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==Primary Author(s)*==
==Primary Author(s)*==


Binu Porath, PhD. Vanderbilt University Medical Center, Nashville, TN
Miguel Gonzalez Mancera, MD
 
Linda D. Cooley, MD, MBA. Children's Mercy Kansas City, Kansas City, MO
==WHO Classification of Disease==
==WHO Classification of Disease==


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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
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|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|''IL3''||''IGH::IL3''||Balanced translocation that joins the IGH enhancer (14q32) to the ''IL3'' gene promoter (5q31.1)<ref>{{Cite journal|last=Meeker|first=T. C.|last2=Hardy|first2=D.|last3=Willman|first3=C.|last4=Hogan|first4=T.|last5=Abrams|first5=J.|date=1990-07-15|title=Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia|url=https://pubmed.ncbi.nlm.nih.gov/2114933|journal=Blood|volume=76|issue=2|pages=285–289|issn=0006-4971|pmid=2114933}}</ref>. This results in IL-3 overexpression that drives the leukemic clone in an autocrine manner and induces eosinophil maturation in the bone marrow and reactive eosinophilia in the peripheral blood<ref>{{Cite journal|last=Knuutila|first=S.|last2=Alitalo|first2=R.|last3=Ruutu|first3=T.|date=1993-12|title=Power of the MAC (morphology-antibody-chromosomes) method in distinguishing reactive and clonal cells: report of a patient with acute lymphatic leukemia, eosinophilia, and t(5;14)|url=https://pubmed.ncbi.nlm.nih.gov/7512364|journal=Genes, Chromosomes & Cancer|volume=8|issue=4|pages=219–223|doi=10.1002/gcc.2870080403|issn=1045-2257|pmid=7512364}}</ref><ref>{{Cite journal|last=Kobayashi|first=Kenichiro|last2=Mizuta|first2=Shumpei|last3=Yamane|first3=Noriko|last4=Ueno|first4=Hiroo|last5=Yoshida|first5=Kenichi|last6=Kato|first6=Itaru|last7=Umeda|first7=Katsutsugu|last8=Hiramatsu|first8=Hidefumi|last9=Suehiro|first9=Minoru|date=2019-01|title=Paraneoplastic hypereosinophilic syndrome associated with IL3-IgH positive acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30207070|journal=Pediatric Blood & Cancer|volume=66|issue=1|pages=e27449|doi=10.1002/pbc.27449|issn=1545-5017|pmid=30207070}}</ref>.||t(5;14)(q31.1;q32)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
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). BCR::ABL1 is generally favorable in CML (add reference).
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
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|<span class="blue-text">EXAMPLE:</span>
|D: This translocation must be detected by karyotyping or FISH
 
T: N/A
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''


P: Too few cases to  accurately assess prognosis
|No (NCCN)
|A small case series suggested an intermediate prognosis, with a poor response to treatment and high levels of measurable residual disease at the end of induction<ref>{{Cite journal|last=Fournier|first=Benjamin|last2=Balducci|first2=Estelle|last3=Duployez|first3=Nicolas|last4=Clappier|first4=Emmanuelle|last5=Cuccuini|first5=Wendy|last6=Arfeuille|first6=Chloé|last7=Caye-Eude|first7=Aurélie|last8=Delabesse|first8=Eric|last9=Bottollier-Lemallaz Colomb|first9=Elodie|date=2019|title=B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL|url=https://pubmed.ncbi.nlm.nih.gov/31921638|journal=Frontiers in Oncology|volume=9|pages=1374|doi=10.3389/fonc.2019.01374|issn=2234-943X|pmc=6914849|pmid=31921638}}</ref>.
|}


Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
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==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==


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==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==


 
No recurrent gene mutations have been described.
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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
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==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


 
The t(5;14)(q31.1;q32) translocation can be detected by karyotyping or FISH; however, in cases with a low blast count, or a cytogenetically cryptic rearrangement may require Next-generation sequencing assays to increase sensitivity<ref>{{Cite journal|last=Guenzel|first=Adam J.|last2=Smadbeck|first2=James B.|last3=Golden|first3=Crystal L.|last4=Williamson|first4=Cynthia M.|last5=Benevides Demasi|first5=Jonna C.|last6=Vasmatzis|first6=George|last7=Pearce|first7=Kathryn E.|last8=Olteanu|first8=Horatiu|last9=Xu|first9=Xinjie|date=2021-08|title=Clinical utility of next generation sequencing to detect IGH/IL3 rearrangements [t(5;14)(q31.1;q32.1)] in B-lymphoblastic leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/33991782|journal=Annals of Diagnostic Pathology|volume=53|pages=151761|doi=10.1016/j.anndiagpath.2021.151761|issn=1532-8198|pmid=33991782}}</ref><ref>{{Cite journal|last=Fournier|first=Benjamin|last2=Balducci|first2=Estelle|last3=Duployez|first3=Nicolas|last4=Clappier|first4=Emmanuelle|last5=Cuccuini|first5=Wendy|last6=Arfeuille|first6=Chloé|last7=Caye-Eude|first7=Aurélie|last8=Delabesse|first8=Eric|last9=Bottollier-Lemallaz Colomb|first9=Elodie|date=2019|title=B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL|url=https://pubmed.ncbi.nlm.nih.gov/31921638|journal=Frontiers in Oncology|volume=9|pages=1374|doi=10.3389/fonc.2019.01374|issn=2234-943X|pmc=6914849|pmid=31921638}}</ref>.
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
==Familial Forms==
==Familial Forms==
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